Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurogenesis continues to occur in the adult hippocampus, although many of the newborn cells degenerate 1-2 weeks after birth. The number and survival of newborn cells are regulated by a variety of environmental stimuli, but very little is known about the intracellular signal transduction pathways that control adult neurogenesis. In the present study, we examine the expression of the phosphorylated cAMP response element-binding protein (pCREB) in immature neurons in adult hippocampus and the role of the cAMP cascade in the survival of new neurons. The results demonstrate that virtually all immature neurons, identified by triple immunohistochemistry for bromodeoxyuridine (BrdU) and polysialic acid-neural cell adhesion molecule (PSA-NCAM), are also positive for pCREB. In addition, upregulation of cAMP (via pharmacological inhibition of cAMP breakdown or by antidepressant treatment) increases the survival of BrdU-positive cells. A possible role for pCREB in the regulation of PSA-NCAM, a marker of immature neurons involved in neuronal remodeling and neurite outgrowth, is supported by cell culture studies demonstrating that the cAMP-CREB pathway regulates the expression of a rate-limiting enzyme responsible for the synthesis of PSA-NCAM. These findings indicate that the cAMP-CREB pathway regulates the survival, and possibly the differentiation and function, of newborn neurons.
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PMID:Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus. 1242 43

The protein acetyltransferases p300 and cAMP response element-binding protein binding protein (CBP) are homologous, ubiquitously expressed proteins that interact with hundreds of proteins involved in transcriptional regulation and are involved globally as transcriptional coregulators. Although these two proteins acetylate and interact with overlapping sets of proteins, we found that p300 and CBP contribute to androgen-induced regulation of distinct sets of genes in C4-2B prostate cancer cells, a model of advanced prostate cancer. CBP cannot compensate for the loss of p300 to support androgen-induced expression of many genes, such as TMPRSS2 and PSA. Global gene expression analysis indicated that 47% of androgen-regulated genes are p300-dependent in these cells, whereas, surprisingly, only 0.3% of them are CBP-dependent. Chromatin immunoprecipitation analysis after depletion of cellular p300 indicated that p300 is required for androgen-induced acetylation of histones H3 and H4, methylation of histone H3 at Lys-4, and recruitment of TATA box binding protein (TBP) and RNA polymerase II, but not recruitment of the androgen receptor, on the TMPRSS2 gene in response to androgen. Thus, p300 is the dominant coregulator of the CBP/p300 pair for androgen-regulated gene expression in C4-2B cells. p300 is required at an early stage of chromatin remodeling and transcription complex assembly after binding of androgen receptor to the gene but before many critical histone modifications occur.
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PMID:Selective roles for cAMP response element-binding protein binding protein and p300 protein as coregulators for androgen-regulated gene expression in advanced prostate cancer cells. 2217 11