PEST Sequence Research Articles

Recent Insights into the Roles of PEST-Containing Nuclear Protein.

PEST-containing nuclear protein (PCNP), a short-lived small nuclear protein with 178 amino acids, is a nuclear protein containing two PEST sequences. PCNP is highly expressed in several malignant tumors such as cervical cancer, rectal cancer, and lung cancer. It is also associated with cell cycle regulation and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Wnt signaling pathways during tumor growth. The present article discuss how PCNP regulates the PI3K/AKT/mTOR and Wnt signaling pathways and related proteins, and the ubiquitination of PCNP regulates tumor cell cycle as well as the progress of the application of PCNP in the pathophysiology and treatment of colon cancer, human ovarian cancer, thyroid cancer, lung adenocarcinoma and oral squamous cell carcinoma. The main relevant articles were retrieved from PubMed, with keywords such as PEST-containing nuclear protein (PCNP), cancer (tumor), and signaling pathways as inclusion/exclusion criteria. Relevant references has been included and cited in the manuscript.

Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation.

IRF2BPL mutation has been associated with a rare neurodevelopmental disorder with abnormal movements, including dystonia. However, the role of IRF2BPL in dystonia remains elusive. We aimed to investigate IRF2BPL mutations in a Taiwanese dystonia cohort. A total of 300 unrelated patients with molecularly unassigned isolated (n = 256) or combined dystonia (n = 44) were enrolled between January 2015 and July 2023. The IRF2BPL variants were analyzed based on whole exome sequencing. The in silico prediction of the identified potential pathogenic variant was performed to predict its pathogenicity. We also compared the clinical and genetic features to previous literature reports. We identified one adolescent patient carrying a de novo heterozygous pathogenic variant of IRF2BPL, c.379C>T (p.Gln127Ter), who presented with generalized dystonia, developmental regression, and epilepsy (0.33% of our dystonia cohort). This variant resides within the polyglutamine (poly Q) domain before the first PEST sequence block of the IRF2BPL protein, remarkably truncating the protein structure. Combined with other patients with IRF2BPL mutations in the literature (n = 60), patients with variants in the poly Q domain have a higher rate of nonsense mutations (p < 0.001) and epilepsy (p = 0.008) than patients with variants in other domains. Furthermore, as our index patient, carriers with substitutions before the first PEST sequence block have significantly older age of onset (p < 0.01) and higher non-epilepsy symptoms, including generalized dystonia (p = 0.003), and ataxia (p = 0.003). IRF2BPL mutation is a rare cause of dystonia in our population. Mutations in different domains of IRF2BPL exhibit different phenotypes.

Stereospecific NANOG PEST Stabilization by Pin1.

NANOG protein levels correlate with stem cell pluripotency. NANOG concentrations fluctuate constantly with low NANOG levels leading to spontaneous cell differentiation. Previous literature implicated Pin1, a phosphorylation-dependent prolyl isomerase, as a key player in NANOG stabilization. Here, using NMR spectroscopy, we investigate the molecular interactions of Pin1 with the NANOG unstructured N-terminal domain that contains a PEST sequence with two phosphorylation sites. Phosphorylation of NANOG PEST peptides increases affinity to Pin1. By systematically increasing the amount of cis PEST conformers, we show that the peptides bind tighter to the prolyl isomerase domain (PPIase) of Pin1. Phosphorylation and cis Pro enhancement at both PEST sites lead to a 5-10-fold increase in NANOG binding to the Pin1 WW domain and PPIase domain, respectively. The cis-populated NANOG PEST peptides can be potential inhibitors for disrupting Pin1-dependent NANOG stabilization in cancer stem cells.

A big data driven vegetation disease and pest region identification method based on self supervised convolutional neural networks and parallel extreme learning machines

A self supervised convolutional neural network-parallel extreme learning machine classification model based on big data is proposed to address the subjectivity and inaccuracy of traditional methods for identifying vegetation pests and diseases that rely on manual observation and empirical judgment. This model is constructed using convolutional neural networks and parallel extreme learning machines, and integrates feature extraction networks with dual attention mechanisms to improve the accuracy of identifying pests and diseases. The model utilized a large amount of big data for training, achieving a recall rate of 98.42 % on multispectral datasets, and an overall classification accuracy of 99.04 %. After optimizing the residual network, the overall accuracy of identifying vegetation pest and disease areas has been further improved to 99.77 %, and the recall rate has also reached 98.91 %. These results indicate that the method proposed in this study has high accuracy and efficiency in the application of big data, can meet the needs of disease and pest identification, and provides effective technical support for the monitoring and prevention of crop diseases and pests, which has important practical significance.

Bortezomib Is Toxic but Induces Neurogenesis and Inhibits TUBB3 Degradation in Rat Neural Stem Cells.

Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

Pest Localization Using YOLOv5 and Classification Based on Quantum Convolutional Network

Pests are always the main source of field damage and severe crop output losses in agriculture. Currently, manually classifying and counting pests is time consuming, and enumeration of population accuracy might be affected by a variety of subjective measures. Additionally, due to pests’ various scales and behaviors, the current pest localization algorithms based on CNN are unsuitable for effective pest management in agriculture. To overcome the existing challenges, in this study, a method is developed for the localization and classification of pests. For localization purposes, the YOLOv5 is trained using the optimal learning hyperparameters which more accurately localize the pest region in plant images with 0.93 F1 scores. After localization, pest images are classified into Paddy with pest/Paddy without pest using the proposed quantum machine learning model, which consists of fifteen layers with two-qubit nodes. The proposed network is trained from scratch with optimal parameters that provide 99.9% classification accuracy. The achieved results are compared to the existing recent methods, which are performed on the same datasets to prove the novelty of the developed model.

Improved abiotic stress tolerance in Arabidopsis by constitutive active form of a banana DREB2 type transcription factor, MaDREB20.CA, than its native form, MaDREB20.

Banana is grown as one of the important fruit crops in tropical and subtropical regions of the world. In this study, we report induced expression of a dehydration responsive element binding 2 (DREB2) gene (MaDREB20) under individual heat, drought, and combined drought and heat stress in root of two banana genotypes Grand Nain (GN) and Hill Banana (HB). Motif analysis of MaDREB20 protein demonstrated the presence of a negative regulatory domain (NRD) or PEST motif between 150 and 184 amino acids. Transgenic Arabidopsis overexpressing MaDREB20 gene showed more survival rate, above-ground biomass, seed yield, leaf relative water content, and proline content but less ion leakage and malonaldehyde content, revealing improved tolerance against heat and drought as well as their combination than the wild-type. Overexpression of MaDREB20.CA (constitutive active form of MaDREB20 after removal of PEST region) showed better abiotic stress tolerance in Arabidopsis than its native form (MaDREB20). Transgenic Arabidopsis overexpressing MaDREB20 and MaDREB20.CA genes appeared to be associated with reduced stomatal densities under normal condition, better regulation of stomatal aperture under drought than in wild-type plants, and differential regulation of downstream target (AtTCH4 and AtIAA1) genes under heat, drought, and combined stress. Taken together, our findings revealed important functions of MaDREB20 in abiotic stress responses in transgenic Arabidopsis and could form a basis for CRISPR/Cas9-mediated removal of its NRD to enhance stress tolerance in banana.

Pest Region Detection in Complex Backgrounds via Contextual Information and Multi-Scale Mixed Attention Mechanism

In precision agriculture, effective monitoring of corn pest regions is crucial to developing early scientific prevention strategies and reducing yield losses. However, complex backgrounds and small objects in real farmland bring challenges to accurate detection. In this paper, we propose an improved model based on YOLOv4 that uses contextual information and attention mechanism. Firstly, a context priming module with simple architecture is designed, where effective features of different layers are fused as additional context features to augment pest region feature representation. Secondly, we propose a multi-scale mixed attention mechanism (MSMAM) with more focus on pest regions and reduction of noise interference. Finally, the mixed attention feature-fusion module (MAFF) with MSMAM as the kernel is applied to selectively fuse effective information from additional features of different scales and alleviate the inconsistencies in their fusion. Experimental results show that the improved model performs better in different growth cycles and backgrounds of corn, such as corn in vegetative 12th, the vegetative tasseling stage, and the overall dataset. Compared with the baseline model (YOLOv4), our model achieves better average precision (AP) by 6.23%, 6.08%, and 7.2%, respectively. In addition, several comparative experiments were conducted on datasets with different corn growth cycles and backgrounds, and the results verified the effectiveness and usability of the proposed method for such tasks, providing technical reference and theoretical research for the automatic identification and control of pests.

Calpain7 negatively regulates human endometrial stromal cell decidualization in EMs by promoting FoxO1 nuclear exclusion via hydrolyzing AKT1.

Endometrial receptivity damage caused by impaired decidualization may be one of the mechanisms of infertility in endometriosis (EMs). Our previous study demonstrated that Calpain-7 (CAPN7) is abnormally overexpressed in EMs. Whether CAPN7 affects the regulation of decidualization and by what mechanism CAPN7 regulates decidualization remains to be determined. In this study, we found CAPN7 expression decreased during human endometrial stromal cell (HESC) decidualization in vitro. CAPN7 negatively regulated decidualization in vitro and in vivo. We also identified one conserved potential PEST sequence in the AKT1 protein and found that CAPN7 was able to hydrolyse AKT1 and enhance AKT1's phosphorylation. Correspondingly, CAPN7 notably promoted the phosphorylation of Forkhead Box O1 (FoxO1), the downstream of AKT1 protein, at Ser319, leading to increased FoxO1 exclusion from nuclei and attenuated FoxO1 transcriptional activity in decidualized HESC. In addition, we detected endometrium CAPN7, p-AKT1, and p-FoxO1 expressions were increased in EMs. These data demonstrate that CAPN7 negatively regulates HESC decidualization in EMs probably by promoting FoxO1's phosphorylation and FoxO1 nuclear exclusion via hydrolyzing AKT1. The dysregulation of CAPN7 may be a novel cause of EMs.

NOTCH1 PEST domain variants are responsive to standard of care treatments despite distinct transformative properties in a breast cancer model.

Activating variants in the PEST region of NOTCH1 have been associated with aggressive phenotypes in human cancers, including triple-negative breast cancer (TNBC). Previous studies suggested that PEST domain variants in TNBC patients resulted in increased cell proliferation, invasiveness, and decreased overall survival. In this study, we assess the phenotypic transformation of activating NOTCH1 variants and their response to standard of care therapies. AAV-mediated gene targeting was used to isogenically incorporate 3 NOTCH1 variants, including a novel TNBC frameshift variant, in two non-tumorigenic breast epithelial cell lines, MCF10A and hTERT-IMEC. Two different variants at the NOTCH1 A2241 site (A2441fs and A2441T) both demonstrated increased transformative properties when compared to a non-transformative PEST domain variant (S2523L). These phenotypic changes include proliferation, migration, anchorage-independent growth, and MAPK pathway activation. In contrast to previous studies, activating NOTCH1 variants did not display sensitivity to a gamma secretase inhibitor (GSI) or resistance to chemotherapies. This study demonstrates distinct transformative phenotypes are specific to a given variant within NOTCH1 and these phenotypes do not correlate with sensitivities or resistance to chemotherapies or GSIs. Although previous studies have suggested NOTCH1 variants may be prognostic for TNBC, our study does not demonstrate prognostic ability of these variants and suggests further characterization would be required for clinical applications.

Biology of PEST-Containing Nuclear Protein: A Potential Molecular Target for Cancer Research.

PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in vital cellular processes like cell proliferation and mediates tumorigenesis. PCNP is a short-living, small nuclear protein of only 178 amino acids with two remarkable PEST sequences that are rich in proline (P), glutamic acid (E), serine (S), and threonine (T). The current understanding of PCNP reveals that PCNP has the ability to interact with cell cycle regulatory proteins; tumor suppressors (p53 and pRB), and promoters (cyclin E and cyclin D) to determine the fate of tissues to facilitate the process of either apoptosis or cell proliferation. In many preclinical studies, it has been evaluated that PCNP expression has associations with the development and progression of various cancers like neuroblastoma, lung adenocarcinoma, and ovarian cancer. Based on these depicted novel roles of PCNP in cell cycleregulation and of PCNP in tumorigenesis, it is logical to consider PCNP as a potential molecular target for cancer research. The aim of the current communication is to present an update on PCNP research and discussion on the potential role of PCNP in cancer development with challenges and opportunities perspectives. Considering the available evidence as a baseline for our statement, we anticipate that in the future, new research insights will strengthen the aim to develop PCNP-based diagnostic and therapeutic approaches that will move the PCNP from the laboratory to the cancer clinic.

Production of antibiotic resistance gene-free urease-deficient recombinant BCG that secretes antigenic protein applicable for practical use in tuberculosis vaccination

Mycobacterium bovis BCG has been the only practical vaccine for tuberculosis. However, BCG cannot fully prevent adult pulmonary tuberculosis. Therefore, the improvement of BCG vaccine is necessary. We previously produced recombinant (r) BCG (BCG-PEST) for the better control of tuberculosis. BCG-PEST was developed by introducing PEST-Heat Shock Protein (HSP)70-Major Membrane Protein (MMP)–II–PEST fusion gene into urease-deficient rBCG using antibiotic-resistant gene for the selection of rBCG. HSP70-MMPII fusion protein is highly immunogenic and PEST sequence was added to enhance processing of the fusion protein. Although BCG-PEST effectively inhibited intrapulmonary growth of Mycobacterium tuberculosis (MTB), BCG with antibiotic-resistant gene is not appropriate for human use. Therefore, we produced antibiotic-resistant gene-free rBCG. We generated leucine-biosynthetic gene (leuD)-deficient BCG and introduced the fusion gene with leuD as the selection marker and named this rBCG as BCG-LeuPH. BCG-LeuPH activated human naïve T cells of both CD4 and CD8 subsets and efficiently inhibited aerosol-challenged MTB in mice. These results indicate that leuD can replace antibiotic-resistant gene for the selection of vaccine candidates of rBCG for human use.

Calpain7 Negatively Regulates Human Endometrial Stromal Cell Decidualization in EMS by Promoting Foxo1 Nuclear Exclusion by Increasing the Phosphorylation of AKT1

Background: Endometrial receptivity damage caused by impaired decidualization may be one of the mechanisms of infertility in endometriosis (EMs). Our previous study demonstrated that CAPN7 is abnormally overexpressed in EMs. Whether CAPN7 affects the regulation of decidualization remains to be determined. Methods: The expression of CAPN7 during decidualization in endometria was examined by IHC and western blotting. The transduction of a CAPN7 recombinant adenovirus into human endometrial stromal cells was performed to investigate relevant decidualization marker genes. An artificial decidualization experiment was performed to study the role of CAPN7 in decidualization in vivo. The potential molecular mechanisms were further confirmed through immunofluorescence and coimmunoprecipitation analyses. IHC analysis was performed to evaluate differentially expressed proteins, including CAPN7, p-AKT1 and p-FoxO1, between the fertile control and EMs groups. Findings: CAPN7 expression decreased during human endometrial stromal cell (HESC) decidualization in vitro. CAPN7 negatively regulated decidualization in vitro and in vivo. In addition, CAPN7 notably promoted the phosphorylation of FoxO1 at Ser319, Ser256 and Thr24, leading to increased FoxO1 exclusion from nuclei in decidualized HESCs. Furthermore, the overexpression of CAPN7 obviously promoted the phosphorylation of AKT1, which is upstream of FoxO1, at Ser473. We also identified one conserved potential PEST sequence in the AKT1 protein and found that CAPN7 was able to hydrolyse AKT1. Interpretation: CAPN7 might serve as a promising therapeutic target for improving endometrial receptivity in women with EMs. Funding: This work was supported by the National Key Research and Development Program of China (2018YFC1004400), the National Natural Science Foundation of China (No. 81070492, No. 81871165 and No. 31872846), a grant from Jiangsu Provincial Key Research and Development (BE2018602), and a special grant for principal investigators from the Health Department of Jiangsu Province (ZDRCA2016070). Declaration of Interest: We declare no potential conflicts of interest concerning the research, authorship, and/or publication of this article. Ethical Approval: All samples were collected with the informed consent of the patients, and approval from the ethics committee was obtained for this study.

Generation of the short TRIM32 isoform is regulated by Lys 247 acetylation and a PEST sequence.

TRIM32 is an E3 ligase implicated in diverse biological pathways and pathologies such as muscular dystrophy and cancer. TRIM32 are expressed both as full-length proteins, and as a truncated protein. The mechanisms for regulating these isoforms are poorly understood. Here we identify a PEST sequence in TRIM32 located in the unstructured region between the RING-BBox-CoiledCoil domains and the NHL repeats. The PEST sequence directs cleavage of TRIM32, generating a truncated protein similarly to the short isoform. We map three lysine residues that regulate PEST mediated cleavage and auto-ubiquitylation activity of TRIM32. Mimicking acetylation of lysine K247 completely inhibits TRIM32 cleavage, while the lysines K50 and K401 are implicated in auto-ubiquitylation activity. We show that the short isoform of TRIM32 is catalytic inactive, suggesting a dominant negative role. These findings uncover that TRIM32 is regulated by post-translational modifications of three lysine residues, and a conserved PEST sequence.

Automatic greenhouse pest recognition based on multiple color space features

Recognition and counting of greenhouse pests are important for monitoring and forecasting pest population dynamics. This study used image processing techniques to recognize and count whiteflies and thrips on a sticky trap located in a greenhouse environment. The digital images of sticky traps were collected using an image-acquisition system under different greenhouse conditions. If a single color space is used, it is difficult to segment the small pests correctly because of the detrimental effects of non-uniform illumination in complex scenarios. Therefore, a method that first segments object pests in two color spaces using the Prewitt operator in I component of the hue-saturation-intensity (HSI) color space and the Canny operator in the B component of the Lab color space was proposed. Then, the segmented results for the two-color spaces were summed and achieved 91.57% segmentation accuracy. Next, because different features of pests contribute differently to the classification of pest species, the study extracted multiple features (e.g., color and shape features) in different color spaces for each segmented pest region to improve the recognition performance. Twenty decision trees were used to form a strong ensemble learning classifier that used a majority voting mechanism and obtains 95.73% recognition accuracy. The proposed method is a feasible and effective way to process greenhouse pest images. The system accurately recognized and counted pests in sticky trap images captured under real greenhouse conditions. Keywords: ensemble learning classifier, greenhouse sticky trap, automated pest recognition and counting, HSI and Lab color spaces, multiple color space features DOI: 10.25165/j.ijabe.20211402.5098 Citation: Yang Z K, Li W Y, Li M, Yang X T. Automatic greenhouse pest recognition based on multiple color space features. Int J Agric & Biol Eng, 2021; 14(2): 188–195.

Ordered structure induced in human c-Myc PEST region upon forming a disulphide bonded dimer

PEST rich protein sequences are intrinsically disordered and serve as degradation hotspots in eukaryotic cells. The structure of PEST degrons in proteins and their mechanism of action remain poorly understood. Deregulation or overexpression of human transcription factor c-Myc causes cancer. The PEST region in c-Myc is implicated for its rapid degradation. Here, we investigate how the structure of 77-residue PEST fragment of c-Myc and its mutant (M1, Trp inserted) are affected by the formation of a covalent dimer. DLS and size exclusion data indicated a ~ 30% increase in Stokes radius upon the formation of the dimer. CD showed an increase in helix and strand content with dimer formation in both Wt and mutant. However, counterintuitively, Trp fluorescence anisotropy decay was marginally faster in the dimer compared to monomer. This anomaly was traced to Trp-Trp Forster resonance energy homotransfer in M1 dimer, suggesting close interaction between two chains in the dimer. Our data suggest that indole rings in the PEST M1 dimer are no further than 24 A apart. These results may hold the key to higher stability of c-Myc in tumours and the poorly understood physiological role of c-Myc oligomer in cells.

Trichoderma reesei Isolated From Austrian Soil With High Potential for Biotechnological Application.

Fungi of the genus Trichoderma are of high importance for biotechnological applications, in biocontrol and for production of homologous and heterologous proteins. However, sexual crossing under laboratory conditions has so far only been achieved with the species Trichoderma reesei, which was so far only isolated from tropical regions. Our isolation efforts aimed at the collection of Trichoderma strains from Austrian soils surprisingly also yielded 12 strains of the species T. reesei, which was previously not known to occur in Europe. Their identity was confirmed with tef1- and rpb2-sequencing and phylogenetic analysis. They could clearly be distinguished from tropical strains including the common laboratory wildtypes by UP-PCR and genetic variations adjacent to the mating type locus. The strains readily mated with reference strains derived from CBS999.97. Secreted cellulase and xylanase levels of these isolates were up to six-fold higher than those of QM6a indicating a high potential for strain improvement. The strains showed different responses to injury in terms of induction of sporulation, but a correlation to alterations in the nox1-gene sequence was not detected. Several synonymous SNPs were found in the sequence of the regulator gene noxR of the soil isolates compared to QM6a. Only in one strain, non-synonymous SNPs were found which impact a PEST sequence of NoxR, suggesting altered protein stability. The availability of sexually fertile strains from middle Europe naturally producing decent amounts of plant cell wall degrading enzymes opens up novel perspectives for non-GMO strain improvement and biological pretreatment of plant biomass for bioethanol production. Moreover, the varied response of these strains to injury in terms of sporulation, which is independent of Nox1 and NoxR suggests that additional regulators impact this phenomenon in T. reesei.

Multifaceted behavior of PEST sequence enriched nuclear proteins in cancer biology and role in gene therapy.

The amino acid sequence enriched with proline (P), glutamic acid (E), serine (S), and threonine (T) (PEST) is a signal-transducing agent providing unique features to its substrate nuclear proteins (PEST-NPs). The PEST motif is responsible for particular posttranslational modifications (PTMs). These PTMs impart distinct properties to PEST-NPs that are responsible for their activation/inhibition, intracellular localization, and stability/degradation. PEST-NPs participate in cancer metabolism, immunity, and protein transcription as oncogenes or as tumor suppressors. Gene-based therapeutics are getting the attention of researchers because of their cell specificity. PEST-NPs are good targets to explore as cancer therapeutics. Insights into PTMs of PEST-NPs demonstrate that these proteins not only interact with each other but also recruit other proteins to/from their active site to promote/inhibit tumors. Thus, the role of PEST-NPs in cancer biology is multivariate. It is hard to obtain therapeutic objectives with single gene therapy. An especially designed combination gene therapy might be a promising strategy in cancer treatment. This review highlights the multifaceted behavior of PEST-NPs in cancer biology. We have summarized a number of studies to address the influence of structure and PEST-mediated PTMs on activation, localization, stability, and protein-protein interactions of PEST-NPs. We also recommend researchers to adopt a pragmatic approach in gene-based cancer therapy.

Zinc Increases ABCA1 by Attenuating Its Clearance Through the Modulation of Calmodulin Activity.

Aim: We previously revealed that Ca++-activated calmodulin binds to ABCA1 by the region near the PEST sequence and retards its calpain-mediated degradation to increase HDL biogenesis. Calmodulin activity is reportedly modulated also by other nutritional divalent cations; thus, we attempted to determine whether Zn++ is involved in the regulation of ABCA1 stability through the modulation of calmodulin activity.Methods: The effects of Zn++ on ABCA1 expression was investigated in J774 mouse macrophage cell-line cells and HepG2 human hepatoma cell-line cells.Results: Zn++ increased ABCA1 expression, not by increasing the mRNA but by attenuating its decay rate, more prominently in the presence of cAMP. Accordingly, it enhanced cell cholesterol release with extracellular apolipo-protein A-I. Calmodulin binding to ABCA1 was increased by Zn++ and Ca++. Zn++ suppressed calpain-mediated hydrolysis of the peptide of ABCA1 cytosolic loop, including the PEST sequence and the calmodulin-binding site, in a calmodulin-dependent fashion, in the presence of the minimum amount of Ca++ to activate calpain, but not calmodulin. Calpain activity was not directly inhibited by Zn++ at the concentration for enhancing calmodulin binding to ABCA1.Conclusion: Nutritional divalent cation Zn++ is involved in the regulation of ABCA1 activity and biogenesis of HDL through the modulation of calmodulin activity. The results were consistent with previous clinical findings that Zn++ increased plasma HDL in the conditions of sympathetic activation, such as type 2 diabetes and chronic hemodialysis.

Progress in the correlation between PTPN12 gene expression and human tumors.

Background:The global morbidity of cancer is rising rapidly. Despite advances in molecular biology, immunology, and cytotoxic and immune-anticancer therapies, cancer remains a major cause of death worldwide. Protein tyrosine phosphatase non-receptor type 12 (PTPN12) is a new member of the cytoplasmic protein tyrosine phosphatase family, isolated from a cDNA library of adult colon tissue. Thus far, no studies have reviewed the correlation between PTPN12 gene expression and human tumors.Methods:This article summarizes the latest domestic and international research developments on how the expression of PTPN12 relates to human tumors. The extensive search in Web of Science and PubMed with the keywords including PTPN12, tumor, renal cell carcinoma, proto-oncogenes, tumor suppressor genes was undertaken.Results:More and more studies have shown that a tumor is essentially a genetic disease, arising from a broken antagonistic function between proto-oncogenes and tumor suppressor genes. When their antagonistic effect is out of balance, it may cause uncontrolled growth of cells and lead to the occurrence of tumors. PTPN12 is a tumor suppressor gene, so inhibiting its activity will lead directly or indirectly to the occurrence of tumors.Conclusion:The etiology, prevention, and treatment of tumors have become the focus of research around the world. PTPN12 is a tumor suppressor gene. In the future, PTPN12 might serve as a novel molecular marker to benefit patients, and even the development of tumor suppressor gene activation agents can form a practical research direction.