FK506-binding Protein Gene Research Articles

Genome-Wide Identification and Bioinformatics Analysis of the FK506 Binding Protein Family in Rice.

The FK506 Binding Protein (FKBP), ubiquitously present across diverse species, is characterized by its evolutionarily conserved FK506 binding domain (FKBd). In plants, evidence suggests that this gene family plays integral roles in regulating growth, development, and responses to environmental stresses. Notably, research on the identification and functionality of FKBP genes in rice remains limited. Therefore, this study utilized bioinformatic tools to identify 30 FKBP-encoding genes in rice. It provides a detailed analysis of their chromosomal locations, evolutionary relationships with the Arabidopsis thaliana FKBP family, and gene structures. Further analysis of the promoter elements of these rice FKBP genes revealed a high presence of stress-responsive elements. Quantitative PCR assays under drought and heat stress conditions demonstrated that genes OsFKBP15-2, OsFKBP15-3, OsFKBP16-3, OsFKBP18, and OsFKBP42b are inducible by these adverse conditions. These findings suggest a significant role for the rice FKBP gene family in stress adaptation. This research establishes a critical foundation for deeper explorations of the functional roles of the OsFKBP genes in rice.

Genome-Wide Identification and Expression Analysis of the Cucumber FKBP Gene Family in Response to Abiotic and Biotic Stresses.

The FKBP (FK506-binding protein) gene family is an important member of the PPlase protease family and plays a vital role during the processes of plant growth and development. However, no studies of the FKBP gene family have been reported in cucumber. In this study, 19 FKBP genes were identified in cucumber, which were located on chromosomes 1, 3, 4, 6, and 7. Phylogenetic analysis divided the cucumber FKBP genes into three subgroups. The FKBP genes in the same subgroup exhibited similar structures and conserved motifs. The cis-acting elements analysis revealed that the promoters of cucumber FKBP genes contained hormone-, stress-, and development-related cis-acting elements. Synteny analysis of the FKBP genes among cucumber, Arabidopsis, and rice showed that 12 kinds of syntenic relationships were detected between cucumber and Arabidopsis FKBP genes, and 3 kinds of syntenic relationships were observed between cucumber and rice FKBP genes. The tissue-specific expression analysis showed that some FKBP genes were expressed in all tissues, while others were only highly expressed in part of the 10 types of tissues. The expression profile analysis of cucumber FKBP genes under 13 types of stresses showed that the CsaV3_1G007080 gene was differentially expressed under abiotic stresses (high temperature, NaCl, silicon, and photoperiod) and biotic stresses (downy mildew, green mottle mosaic virus, Fusarium wilt, phytophthora capsica, angular leaf spot, and root-knot nematode), which indicated that the CsaV3_1G007080 gene plays an important role in the growth and development of cucumber. The interaction protein analysis showed that most of the proteins in the FKBP gene family interacted with each other. The results of this study will lay the foundation for further research on the molecular biological functions of the cucumber FKBP gene family.

Cytoplasmic FKBPs are involved in molting and metamorphosis through regulating the nuclear localization of EcR.

Molting and metamorphosis are important physiological processes in insects that are tightly controlled by ecdysone receptor (EcR) through the 20-hydroxyecdysone (20E) signaling pathway. EcR is a steroid nuclear receptor (SR). Several FK506-binding proteins (FKBPs) have been identified from the mammal SR complex, and are thought to be involved in the subcellular trafficking of SR. However, their roles in insects are poorly understood. To explore whether FKBPs are involved in insect molting or metamorphosis, we injected an FKBP inhibitor (FK506) into a lepidopteran insect, Spodoptera litura, and found that molting was inhibited in 61.11% of the larvae, and that the time for larvae to pupate was significantly extended. A total of 10 FKBP genes were identified from the genome of S.litura and were clustered into 2 distinct groups, according to their subcellular localization, with FKBP13 and FKBP14 belonging to the endoplasmic reticulum (ER) group and with the other members belonging to the cytoplasmic (Cy) group. All the CyFKBPs were significantly upregulated in the prepupal or pupal stages, with the opposite being observed for the ER group members. FK506 completely blocked the transfer of EcR to the nucleus under 20E induction, and significantly downregulated the transcriptional expression of many 20E signaling genes. A similar phenomenon was observed after RNA interference of 2 CyFKBPs (FKBP45 and FKBP12b), but not for FKBP13. Taken together, our data indicate that the cytoplasmic FKBPs, especially FKBP45 and FKBP12b, mediate the nuclear localization of EcR, thereby regulating the 20E signaling and ultimately affecting molting and metamorphosis in insects.

Identification, characterization and spatiotemporal expression analysis of the FKBP family genes in Locusta migratoria

FK506 binding proteins (FKBPs) are a highly-conserved group of proteins known to bind to FK506, an immunosuppressive drug. They play different physiological roles, including transcription regulation, protein folding, signal transduction and immunosuppression. A number of FKBP genes have been identified in eukaryotes; however, very little information about these genes has been reported in Locusta migratoria. Here, we identified and characterized 10 FKBP genes from L. migratoria. Phylogenetic analysis and comparison of domain architectures indicated that the LmFKBP family can be divided into two subfamilies and five subclasses. Developmental and tissue expression pattern analysis revealed that all LmFKBPs transcripts, including LmFKBP46, LmFKBP12, LmFKBP47, LmFKBP79, LmFKBP16, LmFKBP24, LmFKBP44b, LmFKBP53, were periodically expressed during different developmental stages and mainly expressed in the fat body, hemolymph, testis, and ovary. In brief, our work depicts a outline but panoramic picture of LmFKBP family in L. migratoria, and provides a solid foundation to further investigate the molecular functions of LmFKBPs.

Penetrating Exploration of Prognostic Correlations of the FKBP Gene Family with Lung Adenocarcinoma.

The complexity of lung adenocarcinoma (LUAD), the development of which involves many interacting biological processes, makes it difficult to find therapeutic biomarkers for treatment. FK506-binding proteins (FKBPs) are composed of 12 members classified as conservative intracellular immunophilin family proteins, which are often connected to cyclophilin structures by tetratricopeptide repeat domains and have peptidyl prolyl isomerase activity that catalyzes proline from residues and turns the trans form into the cis form. Since FKBPs belong to chaperone molecules and promote protein folding, previous studies demonstrated that FKBP family members significantly contribute to the degradation of damaged, misfolded, abnormal, and foreign proteins. However, transcript expressions of this gene family in LUAD still need to be more fully investigated. In this research, we adopted high-throughput bioinformatics technology to analyze FKBP family genes in LUAD to provide credible information to clinicians and promote the development of novel cancer target drugs in the future. The current data revealed that the messenger (m)RNA levels of FKBP2, FKBP3, FKBP4, FKBP10, FKBP11, and FKBP14 were overexpressed in LUAD, and FKBP10 had connections to poor prognoses among LUAD patients in an overall survival (OS) analysis. Based on the above results, we selected FKBP10 to further conduct a comprehensive analysis of the downstream pathway and network. Through a DAVID analysis, we found that FKBP10 was involved in mitochondrial electron transport, NADH to ubiquinone transport, mitochondrial respiratory chain complex I assembly, etc. The MetaCore pathway analysis also indicated that FKBP10 was involved in "Ubiquinone metabolism", "Translation_(L)-selenoaminoacid incorporation in proteins during translation", and "Transcription_Negative regulation of HIF1A function". Collectively, this study revealed that FKBP family members are both significant prognostic biomarkers for lung cancer progression and promising clinical therapeutic targets, thus providing new targets for treating LUAD patients.

Genome-Wide Identification and Analysis of FKBP Gene Family in Wheat (Triticum asetivum)

FK506-binding protein (FKBP) genes have been found to play vital roles in plant development and abiotic stress responses. However, limited information is available about this gene family in wheat (Triticum aestivum L.). In this study, a total of 64 FKBP genes were identified in wheat via a genome-wide analysis involving a homologous search of the latest wheat genome data, which was unevenly distributed in 21 chromosomes, encoded 152 to 649 amino acids with molecular weights ranging from 16 kDa to 72 kDa, and was localized in the chloroplast, cytoplasm, nucleus, mitochondria, peroxisome and endoplasmic reticulum. Based on sequence alignment and phylogenetic analysis, 64 TaFKBPs were divided into four different groups or subfamilies, providing evidence of an evolutionary relationship with Aegilops tauschii, Brachypodium distachyon, Triticum dicoccoides, Arabidopsis thaliana and Oryza sativa. Hormone-related, abiotic stress-related and development-related cis-elements were preferentially presented in promoters of TaFKBPs. The expression levels of TaFKBP genes were investigated using transcriptome data from the WheatExp database, which exhibited tissue-specific expression patterns. Moreover, TaFKBPs responded to drought and heat stress, and nine of them were randomly selected for validation by qRT-PCR. Yeast cells expressing TaFKBP19-2B-2 or TaFKBP18-6B showed increased influence on drought stress, indicating their negative roles in drought tolerance. Collectively, our results provide valuable information about the FKBP gene family in wheat and contribute to further characterization of FKBPs during plant development and abiotic stress responses, especially in drought stress.

Association of Stress, Glucocorticoid Receptor, and FK506 Binding Protein Gene Polymorphisms With Internalizing Disorders Among HIV-Infected Children and Adolescents From Kampala and Masaka Districts-Uganda.

Children and adolescents living with human immunodeficiency virus (CA-HIV) suffer a considerable burden of internalizing disorders (IDs; depressive and anxiety disorders). Environmental and genetic factors have been reported to influence the vulnerability to IDs in western settings; however, their role among African populations remains inadequately explored. We investigated the individual and interactive effects of stress and single-nucleotide polymorphisms within the FK506 binding protein 5 (rs1360780) and glucocorticoid receptor (rs10482605) genes on ID status in a cohort of CA-HIV in Uganda. We genotyped rs10482605 (309 cases and 315 controls) and rs1360780 (350 cases and 335 controls) among CA-HIV with and without IDs using Kompetitive Allele-Specific PCR. Socio-demographic variables, as well as allele and genotype distributions, were compared between cases and controls using chi-square tests. Genotypes were assessed for Hardy–Weinberg equilibrium. Composite indices of recent and chronic stress classes were also generated. A hierarchical cluster analysis was used to generate cutoff points within each of the indices of recent and chronic stress. Logistic regression was used to assess the association between IDs and each of recent stress, chronic stress, and the investigated genotypes. The interaction effect of chronic/recent stress on the association between each of the polymorphisms and IDs was determined using a likelihood ratio test. We observed no significant association between IDs and rs1360780 and rs10482605 polymorphisms within the FKBP5 and glucocorticoid receptor genes, respectively (P > 0.050). Severe recent stress increased the vulnerability to IDs among CA-HIV (P = 0.001). We did not observe any gene–environment effect on vulnerability to IDs in this population. These findings support the currently held opinion that polymorphisms at single genetic loci only contribute a very small effect to the genetic vulnerability to IDs.

Multi-Omics Analysis of the Expression and Prognosis for FKBP Gene Family in Renal Cancer.

BackgroundThe FK506-binding protein (FKBP) is a family of intracellular receptors that can bind specifically to the immunosuppressant FK506 and rapamycin. Although FKBPs play crucial roles in biological processes and carcinogenesis, their prognostic value and molecular mechanism in clear cell renal cell carcinoma (ccRCC) remain unclear.MethodsUsing pan-cancer data from The Cancer Genome Atlas (TCGA) and public databases, we analyzed the expression and correlation of FKBPs in 33 tumor types. Survival and Cox regression analyses were employed to explore the prognostic value of FKBPs. The relationship with tumor microenvironment and stemness indices was taken into account to evaluate the function of FKBPs. We constructed a risk score model to predict the prognosis of patients with ccRCC. The receiver operating characteristic (ROC) curve was performed to further test the prognostic ability of our model. Nomogram, joint effects analysis, and clinical relevance were performed to assist the clinician. Gene set enrichment analysis (GSEA) and cell line experiments were performed to investigate the function and molecular mechanisms of FKBPs in patients with ccRCC. Paired clinical specimens and multi-omics analysis were used to further validate and explore the factors affecting gene expression in ccRCC patients.ResultsThe expression levels of FKBP10 and FKBP11 were higher in ccRCC tissues than in normal tissues. The alteration in expression may be because of the degree of DNA methylation. Increased expression levels of FKBP10 and FKBP11 were associated with worse overall survival (OS). More importantly, GSEA revealed that FKBP10 is mainly involved in cell metabolism and autophagy, whereas FKBP11 is mainly associated with immune-related biological processes and autophagy. Cell Counting Kit 8 (CCK-8) and Transwell assays revealed that knockdown of FKBP10 and FKBP11 inhibits proliferation, migration, and invasion of the ccRCC cell line.ConclusionFKBP10 and FKBP11 play important roles in ccRCC phenotypes and are potential prognostic markers as well as new therapeutic targets for patients with ccRCC.

Characterization of three FK506-binding proteins in the entomopathogenic fungus Beauveria bassiana

FK506 binding proteins (FKBPs) participate in regulation of diverse biological processes. However, the role of these proteins in insect-pathogenic fungi is far from well understood. To investigate the functions of FKBPs in Beauveria bassiana, a widely used entomopathogenic fungus for control of insect pests, we identify three putative FKBP genes, Bbfkbp12, Bbfkbp15, and Bbfkbp50, in the fungus. Gene-disruption experiments show that loss of Bbfkbp12 results in a significant increase of resistance of B. bassiana against the immunosuppressive compounds FK506 and rapamycin, while loss of Bbfkbp50 leads to the resistance to the ergosterol synthesis inhibitor lovastatin. Transcription assays of calcineurin (CaN)- and mTOR (mammalian target of rapamycin)-downstream target genes confirm that BbFKBP12 is the target of both FK506 and rapamycin, associated with CaN- and mTOR-signal pathways in B. bassiana. GFP-tagging of the proteins shows that BbFKBP12 and BbFKBP15 localize in cytoplasm while BbFKBP50 in nucleus. Our results provide useful information for the study of functions of CaN- and mTOR-mediated signaling, and ergosterol synthesis in the entomopathogenic fungi.

Elective caesarean delivery and offspring’s cognitive impairment: Implications of methylation alteration in hippocampus glucocorticoid signaling genes

Elective caesarean delivery (CD) is an atypical early-life stressful event towards infants. It can pose a long-term effect to children's development by programming hypothalamus-pituitary-adrenal axis. However, the effect of elective CD on offspring’s long-term cognitive function and the potential molecular mechanism remains unknown. In this study, by establishing CD mice model, we found that mice born with CD had lower corticosterone level at birth compared with those born by vaginal delivery (VD). Impairment in learning and memory was observed in CD offspring in adolescence, while the effect did not persist in the adulthood. In hippocampus, the expression of glucocorticoid receptor gene (Nr3c1) and FK506 binding protein gene 5 (Fkbp5) was higher in CD offspring in all postnatal time points. In hippocampus, the average methylation level at nerve growth factor-inducible protein A (NGFI-A) binding sites in exon 17 of Nr3c1, and the methylation in intron 1, intron 5 of Fkbp5 were all lower in CD offspring at infancy. Our data implicated that elective CD will cause delayed but non-permanent cognitive impairment in offspring. Insufficient glucocorticoid function caused by elective CD may bridge the association between this operative delivery mode and offspring’s cognitive impairment. Methylation alterations in key regions of glucocorticoid signaling genes may partially explain the function of glucocorticoid related with elective CD.

Genome-wide analyses of genes encoding FK506-binding proteins reveal their involvement in abiotic stress responses in apple

BackgroundThe FK506-binding proteins (FKBPs) play diverse roles in numerous critical processes for plant growth, development, and abiotic stress responses. However, the FKBP gene family in the important fruit crop apple (Malus × domestica Borkh.) has not been studied as thoroughly as in other species. Our research objective was to investigate the mechanisms by which apple FKBPs enable apple plants to tolerate the effects of abiotic stresses.ResultsUsing bioinformatics-based methods, RT-PCR, and qRT-PCR technologies, we identified 38 FKBP genes and cloned 16 of them in the apple genome. The phylogenetic analysis revealed three major groups within that family. The results from sequence alignments, 3-D structures, phylogenetics, and analyses of conserved domains indicated that apple FKBPs are highly and structurally conserved. Furthermore, genomics structure analysis showed that those genes are also highly and structurally conserved in several other species. Comprehensive qRT-PCR analysis found various expression patterns for MdFKBPs in different tissues and in plant responses to water-deficit and salt stresses. Based on the results from interaction network and co-expression analyses, we determined that the pairing in the MdFKBP62a/MdFKBP65a/b-mediated network is involved in water-deficit and salt-stress signaling, both of which are uniformly up-regulated through interactions with heat shock proteins in apple.ConclusionsThese results provide new insight for further study of FKBP genes and their functions in abiotic stress response and multiple metabolic and physiological processes in apple.

ZmFKBP20-1 improves the drought and salt tolerance of transformed Arabidopsis

FK506-binding proteins (FKBPs), which belong to the peptidyl-prolyl cis/trans isomerase superfamily, are involved in plant response to abiotic stresses. A number of FKBP family genes have been isolated in plants, but little has been reported of FKBP genes in maize. In this study, a drought-induced FKBP gene, ZmFKBP20-1, was isolated from maize and was characterized for its role in stress responses using gene expression, protein subcellular localization, transformation in Arabidopsis, expression patterns of the stress-responsive genes, and physiological parameter analysis. During drought and salt stresses, ZmFKBP20-1 transgenic Arabidopsis plants exhibited enhanced tolerance, which was concomitant with the altered expression of stress/ABA-responsive genes, such as COR15a, COR47, ERD10, RD22, KIN1, ABI1, and ABI2. The resistance characteristics of ZmFKBP20-1 overexpression were associated with a significant increase in survival rate. These results suggested that ZmFKBP20-1 plays a positive role in drought and salt stress responses in Arabidopsis and provided new insights into the mechanisms of FKBP in response to abiotic stresses in plants.

Genome-wide identification and analysis of FK506-binding protein gene family in peach (Prunus persica)

The FKBP protein family has prolyl isomerase activity and is related in function to cyclophilins. FKBPs are known to be involved in many biological processes including hormone signaling, plant growth, and stress responses through a chaperone or an isomerization of proline residues during protein folding. The availability of complete peach genome sequences allowed the identification of 21 FKBP genes by HMMER and BLAST analyses. Scaffold locations of these FKBP genes in the peach genome were determined and the protein domain and motif organization of peach FKBPs were analyzed. The phylogenetic relationships between peach FKBPs were also assessed. The expression profiles of peach FKBP gene results revealed that most peach FKBPs were expressed in all tissues, while a few peach FKBPs were specifically expressed in some of the tissues. This data could contribute to better understanding of the complex regulation of the peach FKBP gene family, and also provide valuable information for further research in peach functional genomics.

Genome-wide identification and analysis of FK506-binding protein family gene family in strawberry (Fragaria × ananassa)

The FK506 binding proteins (FKBPs) are abundant and ubiquitous proteins belonging to the large peptidyl-prolylcis-trans isomerase superfamily. FKBPs are known to be involved in many biological processes including hormone signaling, plant growth, and stress responses through a chaperone or an isomerization of proline residues during protein folding. The availability of complete strawberry genome sequences allowed the identification of 23 FKBP genes by HMMER and blast analysis. Chromosome scaffold locations of these FKBP genes in the strawberry genome were determined and the protein domain and motif organization of FaFKBPs analyzed. The phylogenetic relationships between strawberry FKBPs were also assessed. The expression profiles of FaFKBPs genes results revealed that most FaFKBPs were expressed in all tissues, while a few FaFKBPs were specifically expressed in some of the tissues. These data not only contribute to some better understanding of the complex regulation of the strawberry FKBP gene family, but also provide valuable information for further research in strawberry functional genomics.

Genome-wide analysis and environmental response profiling of the FK506-binding protein gene family in maize (Zea mays L.)

The FK506-binding proteins (FKBPs) belong to the peptidyl-prolyl cis/trans isomerase (PPIase) superfamily, and have been implicated in a wide spectrum of biological processes, including protein folding, hormone signaling, plant growth, and stress responses. Genome-wide structural and evolutionary analyses of the entire FKBP gene family have been conducted in Arabidopsis and rice. In the present study, a genome-wide analysis was performed to identify all maize FKBP genes. The availability of complete maize genome sequences allowed for the identification of 24 FKBP genes. Chromosomal locations in the maize genome were determined and the protein domain and motif organization of ZmFKBPs analyzed. The phylogenetic relationships between maize FKBPs were also assessed. The expression profiles of ZmFKBP genes were measured under different environmental conditions and revealed distinct ZmFKBP gene expression patterns under heat, cold, salt, and drought stress. These data not only contribute to a better understanding of the complex regulation of the maize FKBP gene family, but also provide evidence supporting the role of FKBPs in multiple signaling pathways involved in stress responses. This investigation may provide valuable information for further research on stress tolerance in plants and potential strategies for enhancing maize survival under stressful conditions.

Genome-wide analysis of immunophilin FKBP genes and expression patterns in Zea mays

The receptors for the immunosuppression drugs FK506 and rapamycin are called FKBPs (FK506-binding proteins). FKBPs comprise a large family; they are found in many species, including bacteria, fungi, animals, and plants. As a class of peptidyl-prolyl cis-trans isomerase enzymes, the FKBP genes have been the focus of recent studies on plant stress tolerance and immunology. We identified and analyzed gene families encoding these proteins in maize using computational and molecular biology approaches. Thirty genes were found to encode putative FKBPs according to their FK506-binding domain. The FKBP genes can be classified into single domain and multiple domain members based on the number of the domains. By analysis of the physical locations, the 30 FKBP genes were found to be widely distributed on 10 chromosomes. After analysis of the FKBP phylogenetic tree in the maize genome, we found that the 30 genes revealed two major clades. Gene duplication played a major role in the evolution of FKBP genes, which suggests that the FKBP genes in maize have a pattern significantly different from that of these genes in rice. Based on semi-quantitative RT-PCR, we found that the 30 FKBPs were expressed differently in various tissues in maize, which suggests that FKBP genes play different roles in each tissue. Several FKBPs were expressed at higher levels in roots, indicating that these genes in maize may have similar or overlapping functions.

Relationship between FKBP5 polymorphisms and depression symptoms among kidney transplant recipients

Several polymorphisms in FK506 Binding Protein gene (FKBP5) and a history of child abuse have been shown to be associated with an increased risk for posttraumatic stress disorder (PTSD). It has also been demonstrated that the same polymorphisms of FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. However, there are only limited numbers of studies replicating the polymorphisms as vulnerability factors for the development of mental illnesses, such as PTSD and depression after stressful life event, especially with a specific incidence, such as kidney transplant surgery. A retrospective analysis was conducted using the electronic medical records of 131 adult kidney transplant recipients. Depression severity after kidney transplantation was measured by PHQ-9, and stored blood was genotyped for variants in the Serotonin Transporter (SLC6A4), Brain-Derived Neurotrophic Factor, Catecholamine-O-Methyltransferase, Corticotropin-Releasing Hormone Receptor, and FKBP5 genes. Spearman correlations were used to test for association between genetic variants and depression severity. The rare alleles at three out of four SNPs in FKBP5 (rs1360780, rs9296158, and rs9470080) were associated with increased PHQ-9 scores (P<.05), whereas the last FKBP5 SNP (rs3800373) showed a trend of association (P<.10). All four FKBP5 SNPs are in strong linkage disequilibrium. Although in a subgroup of Caucasian non-Hispanic subjects the association was not statistically significant, the direction of association was consistent with that observed in the entire sample as well as in previous studies. Polymorphisms in genes other than FKBP5 were not associated with PHQ-9 scores. Polymorphisms in FKBP5 may be associated with higher depression scores in kidney transplant recipients.

Genome-wide analysis of genes encoding FK506-binding proteins in rice

The FK506-binding proteins (FKBPs) are a class of peptidyl-prolyl cis/trans isomerase enzymes, some of which can also operate as molecular chaperones. FKBPs comprise a large ubiquitous family, found in virtually every part of the cell and involved in diverse processes from protein folding to stress response. Higher plant genomes typically encode about 20 FKBPs, half of these found in the chloroplast thylakoid lumen. Several FKBPs in plants are regulators of hormone signalling pathways, with important roles in seed germination, plant growth and stress response. Some FKBP isoforms exists as homologous duplicates operating in finely tuned mechanisms to cope with abiotic stress. In order to understand the roles of the plant FKBPs, especially in view of the warming environment, we have identified and analysed the gene families encoding these proteins in rice using computational approaches. The work has led to identification of all FKBPs from the rice genome, including novel high molecular weight forms. The rice FKBP family appears to have evolved by duplications of FKBP genes, which may be a strategy for increased stress tolerance.

FKBP5, SERT and COMT mRNA expressions in the peripheral leukocytes during menstruation cycle in healthy reproductive females

There have been several evidences that the mRNA expressions in the peripheral leukocytes may indicate not only physical but also psychological states. The purpose of this study is whether the mRNA expressional changes in the leukocytes are related to the mental states across the menstrual cycle in reproductive healthy female subjects. Thirty-eight female subjects (22.4+/-1.4 year-old) were participated in this study at three menstruation cycle periods (menstrual, follicular and luteal phase). The FKBP5 (FK506-binding protein gene), SERT (serotonin transporter gene) and COMT (catechol-o-methyltransferase gene) mRNA expressions in the leukocytes were determined with hormonal data. The psychological changes were assessed with self-rating hospital anxiety and depression scale (HADS). Only one thirds of subjects (n=12) had regular menstrual cycles during the experiment. So we analyzed the data from these 12 subjects. The anxiety score of each subject was changed across the menstrual cycle (Friedman test: P<0.05). The FKBP5 mRNA expression was significantly lower in the follicular phase than in the other phases but no changes were seen in either SERT or COMT mRNA expressions among the phases. In conclusion, there are differences of HADS anxiety score and FKBP5 mRNA expression in the leukocytes across the menstrual cycle but there is no correlation between anxiety scores and FKBP5 mRNA.

Evolution of the 12 kDa FK506‐binding protein gene

The FKBPs (FK506-binding proteins) belong to a ubiquitous family of proteins that are found in a wide range of taxonomic groups. These proteins participate in a variety of pathways, including protein folding, down-regulation of T-cell activation and inhibition of cell-cycle progression. A cDNA encoding the 12 kDa FKBP gene orthologue (FKBP12) in Bombyx mori was been isolated from both Bm-5 cultured cells and silk-gland tissue. Using the FKBP12 cDNA in combination with the B. mori 6x whole-genome shotgun database, we were able to identify the FKBP12 gene, as well as the positions of its intron-exon junctions. FKBP12 exon sizes and intronic positions are highly conserved among FKBP12 orthologues in 24 diverse genomes. Comparison of 41 FKBP12 genes revealed several intronic insertion and deletion events throughout evolution. In addition, paralogous FKBP12 isoforms were identified in all 12 vertebrate genomes. Both structural and phylogenetics analyses suggest that the isoforms may be evolving independently, possibly due to the distinct functional roles played by each paralogue.