Growth-related Proteins Research Articles

Akt-Mediated YB-1 Phosphorylation Activates Translation of Silent mRNA Species

YB-1 is a broad-specificity RNA-binding protein that is involved in regulation of mRNA transcription, splicing, translation, and stability. In both germinal and somatic cells, YB-1 and related proteins are major components of translationally inactive messenger ribonucleoprotein particles (mRNPs) and are mainly responsible for storage of mRNAs in a silent state. However, mechanisms regulating the repressor activity of YB-1 are not well understood. Here we demonstrate that association of YB-1 with the capped 5' terminus of the mRNA is regulated via phosphorylation by the serine/threonine protein kinase Akt. In contrast to its nonphosphorylated form, phosphorylated YB-1 fails to inhibit cap-dependent but not internal ribosome entry site-dependent translation of a reporter mRNA in vitro. We also show that similar to YB-1, Akt is associated with inactive mRNPs and that activated Akt may relieve translational repression of the YB-1-bound mRNAs. Using Affymetrix microarrays, we found that many of the YB-1-associated messages encode stress- and growth-related proteins, raising the intriguing possibility that Akt-mediated YB-1 phosphorylation could, in part, increase production of proteins regulating cell proliferation, oncogenic transformation, and stress response.

Bacterial genome adaptation to niches: divergence of the potential virulence genes in three Burkholderia species of different survival strategies.

BackgroundTwo closely related species Burkholderia mallei (Bm) and Burkholderia pseudomallei (Bp) are serious human health hazards and are potential bio-warfare agents, whereas another closely related species Burkholderia thailandensis (Bt) is a non-pathogenic saprophyte. To investigate the genomic factors resulting in such a dramatic difference, we first identified the Bm genes responsive to the mouse environment, and then examined the divergence of these genes in Bp and Bt.ResultsThe genes down-expressed, which largely encode cell growth-related proteins, are conserved well in all three species, whereas those up-expressed, which include potential virulence genes, are less well conserved or absent notably in Bt. However, a substantial number of up-expressed genes is still conserved in Bt. Bm and Bp further diverged from each other in a small number of genes resulting from unit number changes in simple sequence repeats (ssr) in the homologs.ConclusionOur data suggest that divergent evolution of a small set of genes, rather than acquisition or loss of pathogenic islands, is associated with the development of different life styles in these bacteria of similar genomic contents. Further divergence between Bm and Bp mediated by ssr changes may reflect different adaptive processes of Bm and Bp fine-tuning into their host environments.

Effects of Intrauterine Growth Retardation on Development of the Gastrointestinal Tract in Neonatal Pigs

Background: Intrauterine growth retardation (IUGR) is a common problem in human and other species and increases the risk of death of the fetus and newborn during the perinatal period. Objectives: This study was conducted to examine the influences of intrauterine growth retardation (IUGR) on development of the gastrointestinal tract in newborn pigs. Methods: Ten animals from five litters were divided into five piglets with IUGR and five with normal birth-weight (NW). The IUGR category comprised animals with a birth weight 2 SD below the mean birth weight of the total population, while the NW category included animals with a birth weight within one SD of the mean birth weight in the total population. Animals were anesthetized and sampled within 2–4 h after birth and without suckling. The morphological changes of intestine and stomach of IUGR piglets were compared with NW ones. The expressions of IGF-I and receptors for growth hormone and insulin in intestinal mucosa were semiquantified using reverse transcription PCR. Results: The results of our study indicated that the weights of the stomach, small intestine and small intestinal mucosa were significantly lower in IUGR compared with NW piglets (p < 0.01). In addition, the lengths of the small intestine and colon in IUGR pigs were also significantly less than those of NW (p < 0.05). Furthermore, insulin-like growth factor-I (IGF-I) mRNA level in intestinal mucosa of IUGR piglets was increased significantly (p < 0.05), and the expression mRNA levels of insulin receptor and growth hormone (GH) receptor in the mucosa in IUGR piglets showed a tendency to be lower (p = 0.17 and p = 0.11, respectively) than those of the NW animals. Conclusion: We conclude from the data that IUGR affects intestinal growth and morphology and is in associated with altered gene expression of growth-related proteins. We speculate that the morphological change and associated altered endocrine homeostasis contribute to lower growth rates of pigs affected by IUGR.

The role of the AU-rich elements of mRNAs in controlling translation

Adenosine- and uridine-rich elements (AREs) located in 3'-untranslated regions are the best-known determinants of RNA instability. These elements have also been shown to control translation in certain mRNAs, including mRNAs for prominent pro-inflammatory and tumor growth-related proteins, and physiological anti-inflammatory processes that target ARE-controlled translation of mRNAs coding for pro-inflammatory proteins have been described. A major research effort is now being made to understand the mechanisms by which the translation of these mRNAs is controlled and the signalling pathways involved. This review focuses on the role of ARE-containing gene translation in inflammation, and the disease models that have improved our understanding of ARE-mediated translational control.

Expression of MAP1B protein and its phosphorylated form MAP1B-P in the CNS of a continuously growing fish, the rainbow trout

Microtubule-associated protein-1B (MAP1B), and particularly its phosphorylated isoform MAP1B-P, play an important role in axonal outgrowth during development of the mammalian nervous system and have also been shown to be associated with axonal plasticity in the adult. Here, we used antibodies and mRNA probes directed against mammalian MAP1B to extend our analysis to fish species, trout ( Oncorhynchus mykiss), at different stages of development. The specificity of the cross-reaction of our anti-total-MAP1B/MAP1B-P antibodies was confirmed by Western blotting. Trout MAP1B-like proteins exhibited about the same apparent molecular weight (320 kDa) as rat-MAP1B. Immunohistochemistry and in situ hybridization analysis performed on hindbrain and spinal cord revealed the presence of MAP1B in neurons and some glial subpopulations. Primary sensory neurons and motoneurons maintain high levels of MAP1B expression from early stages throughout adulthood, as has been shown for mammals. Unlike mammals, however, MAP1B and axon-specific MAP1B-P continue to be strongly expressed by hindbrain neurons projecting into spinal cord, with the important exception of Mauthner cells. MAP1B/MAP1B-P immunostaining were also detected elsewhere within the brain, including axons of the retino-tectal projection. This obvious difference between adult fish and mammals is likely to reflect the capacity of fish for continued growth and regeneration. Our results suggest that MAP1B/MAP1B-P expression is generally maintained in neurons known to regenerate after axotomy. The regenerative potential of the adult nervous system may in fact depend on continued expression of neuron-intrinsic growth related proteins, a feature of MAP1B that appears phylogenetically conserved.

Anti-inflammatory and growth-stimulating effects precede nutritional restitution during enteral feeding in Crohn disease.

Exclusive enteral feeding reduces inflammation and improves well being, nutrition and growth in children with active Crohn disease. Whether improved growth and increases in growth-related proteins are a consequence of improved nutrition or a reduced inflammation is not known. This study was undertaken to test the hypothesis that changes in growth-related proteins are related to decreased inflammation, rather than improvement in nutritional status. Twelve children with active Crohn disease treated for 6-weeks with exclusive enteral feeding were studied at days 0, 3, 7, 14, 21, 28, and 56. The Paediatric Crohn's Disease Activity Index (PCDAI), weight, triceps skinfold thickness, and midupper arm circumference were recorded. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), insulin-like growth factor (IGF-I), IGF-binding protein (IGFBP-3), and leptin were measured at each visit. Wilcoxon matched-pairs signed-rank test was used to compare day 0 with follow-up data. Significant improvements (P < 0.05) occurred by day 3 in inflammatory parameters (ESR, IL-6) and by day 7 in PCDAI, CRP, and IGF-I. These changes preceded any significant changes in nutritional parameters (weight-for-age Z score and midupper arm circumference day 14, triceps skinfold thickness day 21). Early increases in IGF-I during treatment of Crohn disease are attributable to the anti-inflammatory effect of the enteral feed rather than nutritional restitution.

Plasticity following Injury to the Adult Central Nervous System: Is Recapitulation of a Developmental State Worth Promoting?

The adult central nervous system (CNS) appears to initiate a transient increase in plasticity following injury, including increases in growth-related proteins and generation of new cells. Recent evidence is reviewed that the injured adult CNS exhibits events and patterns of gene expression that are also observed during development and during regeneration following damage to the mature peripheral nervous system (PNS). The growth of neurons during development or regeneration is correlated, in part, with a coordinated expression of growth-related proteins, such as growth-associated-protein-43 (GAP-43), microtubule-associated-protein-1B (MAP1B), and polysialylated-neural-cell-adhesion-molecule (PSA-NCAM). For each of these proteins, evidence is discussed regarding its specific role in neuronal development, signals that modify its expression, and reappearance following injury. The rate of adult hippocampal neurogenesis is also affected by numerous endogenous and exogenous factors including injury. The continuing study of developmental neurobiology will likely provide further gene and protein targets for increasing plasticity and regeneration in the mature adult CNS.

Manipulating transmitter release at the neuromuscular junction of neonatal rats alters the expression of ChAT and GAP-43 in motoneurons

During early postnatal development, motoneurons innervating rat hindlimb muscles die following injury to the sciatic nerve. However, prematurely enhancing transmitter release from nerve terminals of neonatal rats renders motoneurons less vulnerable to nerve injury, whereas reducing transmitter release increases their susceptibility to injury. Thus, alterations in transmitter release may have an influence on motoneuron phenotype. Here we investigated the relationship between the vulnerability of motoneurons to injury, and the expression of proteins associated with axonal growth and neuromuscular transmission. We examined the effect of agents that affect transmitter release from nerve terminals and that have been shown to influence the expression of transmitter and growth related proteins in developing motoneurons in response to nerve injury. In newborn rats, implants containing either 4-aminopyridine (4-AP), to increase transmitter release, or magnesium sulphate (MgSO 4), to decrease release, were applied to the soleus muscle in one hindlimb. The effect of these treatments on the activity of choline acetyltransferase (ChAT) in nerve terminals in the soleus muscle was measured using a radiochemical assay. Levels of GAP-43 in sciatic nerve were also assessed, by Western blot analysis. The results showed that during normal development, there was a gradual increase in ChAT activity during the second week of postnatal development, whereas GAP-43 levels declined sharply between postnatal days 12–14. However, following 4-AP treatment, there was a dramatic increase in ChAT activity in nerve terminals contacting the treated soleus muscles and the levels of GAP-43 in the sciatic nerve declined at an earlier age than normal. Conversely, following treatment with MgSO 4 the normal increase in ChAT activity that occurs during the second postnatal week was delayed, and GAP-43 levels in the sciatic nerve were maintained for significantly longer than normal. Thus, manipulating transmitter release from nerve terminals in neonatal rats alters the normal pattern of expression of transmitter and growth related proteins in developing motoneurons. This alteration in protein expression may influence both the maturation of motoneurons and their ability to withstand nerve injury.

Autoprotection against acetaminophen toxicity in cultured rat hepatocytes: the effect of pretreatment and growth factors.

To evaluate the effect of acetaminophen pretreatment and growth factors on acetaminophen hepatotoxicity in cultured rat hepatocytes, rat hepatocytes in primary culture were exposed to acetaminophen 8 mM after pretreatment with either acetaminophen 1 mM, treatment with growth factors (EGF and HGF), or no treatment. Growth response was measured by changes in DNA, [3H]thymidine incorporation and mRNA of growth related proteins, cell damage by leakage of LDH to the medium and changes in ATP, and protection against toxicity by changes in glutathione, cytochrome p450 and the expression of glutathione-S-transferase and Cyp1A2. Pretreatment with acetaminophen induced growth response, weaker than that of growth factors, but pretreatment and growth factors reduced cell damage equally effectively. Glutathione and glutathione-S-transferase increased more by growth factors than by pretreatment, but both conditions reduced Cyp1A2 to near zero. Pretreatment and growth factors protect against acetaminophen toxicity by suppressing the expression of Cyp1A2, thereby reducing the production of the intermediate N-acetyl-p-benzoquinone imine (NAPQI). Suppression of Cyp1A2 expression by pretreatment is assumed to be due to a growth-stimulating effect of low concentrations of acetaminophen.

Insulin-like growth factor system gene expression in women with type 2 diabetes and breast cancer

Background/Aims: A twofold increased risk for breast cancer has been reported recently for women with late onset diabetes. Most studies showed that there were differences in serum concentrations of insulin-like...

Current pharmacotherapy for the treatment of severe burns

The pharmacotherapy of burn care has evolved from the first topical antibiotics instituted > 30 years ago. These have helped greatly to reduce the incidence of burn wound sepsis, but a better understanding of the principles of burn care has resulted in earlier burn wound excision and complete coverage with autograft, cadaver skin, synthetic dressings, and amnion. This has markedly reduced septic complications and ameliorated the hypermetabolic response to burn injury. The hypermetabolic response, which is mediated by hugely increased levels of circulating catecholamines, prostaglandins, glucagon and cortisol, causes profound skeletal muscle catabolism, immune deficiency, peripheral lipolysis, reduced bone mineralisation, reduced linear growth, and increased energy expenditure. Supportive therapy and pharmacological manipulation, acutely and during rehabilitation, with growth hormone, insulin and related proteins, oxandrolone and propranolol can ameliorate the hypermetabolic response, improving survival and long-term outcome. Despite judicious use of topical and systemic antibiotics, opportunistic nosocomial bacterial resistance threatens to annul the improved survival of patients with severe burns. Patterns of emerging resistance encountered in burn units need to be considered, in light of a decreasing antibiotic armamentarium. A holistic approach to pharmacotherapy of severely burned patients including current practice in antimicrobial control, analgesia, sedation, and anxiety management is required. Current therapy of frequently encountered problems, such as post-burn pruritus, prophylaxis of deep venous thrombosis and peptic ulceration, and pharmacological manipulation of inhalation injury in the burned patient is described. Current pharmacotherapy to ameliorate psychosocial problems associated with burns such as acute stress disorder, depression and post traumatic stress disorder are discussed. Better analgesics, newer antibiotics and immune stimulating drugs are required to reduce mortality and morbidity in large burns.

Gene expression profiling by DNA microarray analysis in mouse embryonic fibroblasts transformed by rasV12 mutated protein and the E1A oncogene

BackgroundRas is an area of intensive biochemical and genetic studies and characterizing downstream components that relay ras-induced signals is clearly important. We used a systematic approach, based on DNA microarray technology to establish a first catalog of genes whose expression is altered by ras and, as such, potentially involved in the regulation of cell growth and transformation.ResultsWe used DNA microarrays to analyze gene expression profiles of rasV12/E1A-transformed mouse embryonic fibroblasts. Among the ~12,000 genes and ESTs analyzed, 815 showed altered expression in rasV12/E1A-transformed fibroblasts, compared to control fibroblasts, of which 203 corresponded to ESTs. Among known genes, 202 were up-regulated and 410 were down-regulated. About one half of genes encoding transcription factors, signaling proteins, membrane proteins, channels or apoptosis-related proteins was up-regulated whereas the other half was down-regulated. Interestingly, most of the genes encoding structural proteins, secretory proteins, receptors, extracellular matrix components, and cytosolic proteins were down-regulated whereas genes encoding DNA-associated proteins (involved in DNA replication and reparation) and cell growth-related proteins were up-regulated. These data may explain, at least in part, the behavior of transformed cells in that down-regulation of structural proteins, extracellular matrix components, secretory proteins and receptors is consistent with reversion of the phenotype of transformed cells towards a less differentiated phenotype, and up-regulation of cell growth-related proteins and DNA-associated proteins is consistent with their accelerated growth. Yet, we also found very unexpected results. For example, proteases and inhibitors of proteases as well as all 8 angiogenic factors present on the array were down-regulated in transformed fibroblasts although they are generally up-regulated in cancers. This observation suggests that, in human cancers, proteases, protease inhibitors and angiogenic factors could be regulated through a mechanism disconnected from ras activation.ConclusionsThis study established a first catalog of genes whose expression is altered upon fibroblast transformation by rasV12/E1A. This catalog is representative of the genome but not exhaustive, because only one third of expressed genes was examined. In addition, contribution to ras signaling of post-transcriptional and post-translational modifications was not addressed. Yet, the information gathered should be quite useful to future investigations on the molecular mechanisms of oncogenic transformation.

Patterns of gene expression in atrophying skeletal muscles: response to food deprivation.

During fasting and many systemic diseases, muscle undergoes rapid loss of protein and functional capacity. To define the transcriptional changes triggering muscle atrophy and energy conservation in fasting, we used cDNA microarrays to compare mRNAs from muscles of control and food-deprived mice. Expression of >94% of genes did not change, but interesting patterns emerged among genes that were differentially expressed: 1) mRNAs encoding polyubiquitin, ubiquitin extension proteins, and many (but not all) proteasome subunits increased, which presumably contributes to accelerated protein breakdown; 2) a dramatic increase in mRNA for the ubiquitin ligase, atrogin-1, but not most E3s; 3) a significant suppression of mRNA for myosin binding protein H (but not other myofibrillar proteins) and IGF binding protein 5, which may favor cell protein loss; 4) decreases in mRNAs for several glycolytic enzymes and phosphorylase kinase subunits, and dramatic increases in mRNAs for pyruvate dehydrogenase kinase 4 and glutamine synthase, which should promote glucose sparing and gluconeogenesis. During fasting, metallothionein mRNA increased dramatically, mRNAs for extracellular matrix components fell, and mRNAs that may favor cap-independent mRNA translation rose. Significant changes occurred in mRNAs for many growth-related proteins and transcriptional regulators. These transcriptional changes indicate a complex adaptive program that should favor protein degradation and suppress glucose oxidation in muscle. Similar analysis of muscles atrophying for other causes is allowing us to identify a set of atrophy-specific changes in gene expression.

Long-lasting sprouting and gene expression changes induced by the monoclonal antibody IN-1 in the adult spinal cord.

Lesion-induced plasticity of the rat corticospinal tract (CST) decreases postnatally, simultaneously with myelin appearance. In adult rats, compensatory sprouting can be induced by the monoclonal antibody (mAb) IN-1 raised against the growth inhibitory protein Nogo-A. In this study, we examined separately the fate of sensory and motor corticospinal fibers after mAb IN-1 application. Intact adult rats treated with the IN-1 antibody exhibited an increase of aberrant CST projections, i.e., sensory fibers projecting into the ventral horn and motor fibers projecting dorsally. Unilateral lesion of the CST [pyramidotomy (PTX)] in the presence of mAb IN-1 triggered a progressive reorganization of the sprouting of the remaining CST across the midline, with sensory fibers projecting gradually into the denervated dorsal horn and motor fibers projecting into the denervated ventral horn. In unilaterally denervated spinal cords, aberrant sprouts were only transient and disappeared by 6 weeks, whereas midline crossing fibers ending in the appropriate target region were stabilized and persisted over the entire study period. Within the spinal cord, IN-1 antibody treatment was associated with upregulation of growth factors (BDNF, VEGF), growth-related proteins (actin, myosin, GAP-43), and transcription factors (STATs), whereas pyramidotomy induced an enhanced expression of guidance molecules (semaphorins and slits) as well as neurotrophic factors (BDNF, IGFs, BMPs). These gene expression changes may contribute to attraction, guidance, and stabilization of sprouting CST fibers.

Non-genomic stimulation of tyrosine phosphorylation cascades by 1,25(OH)(2)D(3) by VDR-dependent and -independent mechanisms in muscle cells.

Studies with different cell types have shown that modulation of various of the fast as well as long-term responses to 1,25(OH)(2)D(3) depends on the activation of tyrosine kinase pathways. Recent investigations of our laboratory have demonstrated that 1,25(OH)(2)D(3) rapidly stimulates in muscle cells tyrosine phosphorylation of PLC-gamma and the growth-related proteins MAPK and c-myc. We have now obtained evidence using antisense technology indicating that VDR-dependent activation of Src mediates the fast stimulation of tyrosine phosphorylation of c-myc elicited by the hormone. This non-genomic action of 1,25(OH)(2)D(3) requires tyrosine phosphorylation of the VDR. Immunoprecipitation under native conditions coupled to Western blot analysis revealed 1,25(OH)(2)D(3)-dependent formation of complexes between Src and the VDR and c-myc. However, the activation of MAPK by the hormone was only partially mediated by the VDR and required in addition increased PKC and intracellular Ca(2+). Following its phosphorylation, MAPK translocates into the nucleus where it regulates c-myc transcription. Altogether these results indicate that tyrosine phosphorylation plays a role in the stimulation of muscle cell growth by 1,25(OH)(2)D(3). Data were also obtained involving tyrosine kinases and the VDR in hormone regulation of the Ca(2+) messenger system by mediating the stimulation of store-operated calcium (SOC; TRP) channels. Congruent with this action, 1,25(OH)(2)D(3) induces a rapid translocation of the VDR to the plasma cell membrane which can be blocked by tyrosine kinase inhibitors. Of mechanistic relevance, an association between the VDR and TRP proteins with the participation of the scaffold protein INAD was shown.

Augmentation of Wound Healing with Translation Initiation Factor eIF4E mRNA

Background. Initiation of translation is the rate-limiting step in protein synthesis; eIF4E increases translational efficiency by facilitating ribosome scanning. eIF4E is present in cells in rate-limiting amounts; chronic overexpression of eIF4E causes cell transformation by upregulating growth-related proteins. Biolistic delivery of epidermal growth factor (EGF) increases wound healing; transiently increasing wound eIF4E levels with biolistic mRNA transmission may further augment wound healing without oncogenesis.Patients and methods. Midline fascial wounds were created in rats and biolistically treated with gold particles carrying mRNA encoding for hEGF with or without eIF4E prior to suture closure; control animals received blank bullets. The animals were sacrificed at 7 or 14 days for determination of peak wound bursting strength on a tensiometer. Results are expressed as means ± standard deviation; statistics were via analysis of variance.Results.Conclusions. Simultaneous biolistic delivery of EGF mRNA with eIF4E mRNA significantly increases wound breaking strength compared to that in control animals or treatment with EGF mRNA alone without risk of cellular transformation. Further studies of translational activation to augment wound healing are warranted.

Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface.

NOX proteins are growth-related cell surface proteins that catalyze both hydroquinone or NADH oxidation and protein disulfide interchange and exhibit prion-like properties. The two enzymatic activities alternate to generate a regular period length of about 24 min. Here we report the expression, cloning, and characterization of a tumor-associated NADH oxidase (tNOX). The cDNA sequence of 1830 bp is located on gene Xq25-26 with an open reading frame encoding 610 amino acids. The activities of the bacterially expressed tNOX oscillate with a period length of 22 min as is characteristic of tNOX activities in situ. The activities are inhibited completely by capsaicin, which represents a defining characteristic of tNOX activity. Functional motifs identified by site-directed mutagenesis within the C-terminal portion of the tNOX protein corresponding to the processed plasma membrane-associated form include quinone (capsaicin), copper and adenine nucleotide binding domains, and two cysteines essential for catalytic activity. Four of the six cysteine to alanine replacements retained enzymatic activity, but the period lengths of the oscillations were increased. A single protein with two alternating enzymatic activities indicative of a time-keeping function is unprecedented in the biochemical literature.

Liver gene regulation in rats following both 70 or 90% hepatectomy and endotoxin treatment.

The metabolic state effect of liver failure on liver gene regulation was evaluated in a rat model. Following 70 or 90% hepatectomy and lipopolysaccharide or vehicle treatment at intervals up to 24 h, the liver remnants were analyzed for mRNA levels for acute-phase, liver-specific and growth-related proteins. After 70% hepatectomy mRNA for alpha 1-acid glycoprotein, alpha 2-macroglobulin, thiostatin and fibrinogen, haptoglobin increased three- to sevenfold (P < 0.05), and mRNA for cyclin D and histone 3 increased seven- and 15-fold (P < 0.05), respectively. After lipopolysaccharide injection and 70% hepatectomy were done, mRNA for acute-phase proteins raised significantly (P < 0.05), more to five to 20-fold, while mRNA for growth-related proteins raised significantly (P < 0.05) less to three- to fourfold. After 90% hepatectomy, acute-phase protein mRNA increased five- to ninefold (P < 0.05) more than after 70% hepatectomy, while mRNA for histone 3 and cyclin D did not increase within 24 h, which indicates a delayed growth after 90% hepatectomy. In 90% of hepatectomized rats treated with lipopolysaccharide, acute-phase protein mRNA raised three- to sixfold (P < 0.05) less than after vehicle treatment. In endotoxemia from liver failure, the synthesis of acute-phase proteins is upregulated by gene regulation at the expense of that for regeneration, which may be an appropriate response for immediate survival. In severe liver failure, endotoxin may interfere with the appropriate gene regulation.

Mechanism of polyamine regulation of oncogenes and growth related proteins

Mechanism of polyamine regulation of oncogenes and growth related proteins

Mechanism of polyamine regulation of oncogenes and growth related proteins

Mechanism of polyamine regulation of oncogenes and growth related proteins