Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human T-cell leukemia virus type I (HTLV-I) transactivator protein Tax is critical for the activation of viral gene expression and the transformation of T-lymphocytes. Tax activation of HTLV-I gene expression is mediated by three highly homologous regulatory elements known as 21 bp repeats which bind the transcription factor CREB. Questions remain about the mechanism by which Tax can stimulate CREB binding, whether Tax alters CREB binding affinity, what specific sequences in the HTLV-I 21 bp repeat mediate ternary complex formation, and if the ternary complex comprised of Tax and CREB can recruit coactivators such as CBP. To address these points, we used immobilized templates containing either the HTLV-I 21 bp repeats or the somatostatin CRE to assay Tax association with ATF/CREB family members. Tax formed a stable ternary complex on each of the 21 bp repeats with the transcription factor CREB but not related ATF/CREB proteins. In contrast, Tax did not form a similar complex on the CREB binding site in the somatostatin promoter. The formation of this complex was dependent on 3' sequences flanking the CREB binding site within each of the 21 bp repeats and resulted in marked increases in CREB association and binding affinity. Tax increased the binding of phosphorylated CREB to the 21 bp repeat resulting in increased association of the coactivator CBP. However, Tax did not form a complex on the somatostatin CRE in the presence of either phosphorylated or non-phosphorylated CREB and it did not stimulate CBP association to this element. These studies extend previous work and demonstrate how specific DNA sequences flanking the CREB binding site regulate the formation of a stable ternary complex that is able to more efficiently recruit the coactivator CBP.
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PMID:HTLV-1 21 bp repeat sequences facilitate stable association between Tax and CREB to increase CREB binding affinity. 895 Feb 64

In a transgenic mouse model of the neurodegenerative disorder Huntington's disease (HD), age-dependent neurologic defects are accompanied by progressive alterations in glucose tolerance that culminate in the development of diabetes mellitus and insulin deficiency. Pancreatic islets from HD transgenic mice express reduced levels of the pancreatic islet hormones insulin, somatostatin, and glucagon and exhibit intrinsic defects in insulin production. Intranuclear inclusions accumulate with aging in transgenic pancreatic islets, concomitant with the decline in glucose tolerance. HD transgenic mice develop an age-dependent reduction of insulin mRNA expression and diminished expression of key regulators of insulin gene transcription, including the pancreatic homeoprotein PDX-1, E2A proteins, and the coactivators CBP and p300. Disrupted expression of a subset of transcription factors in pancreatic beta cells by a polyglutamine expansion tract in the huntingtin protein selectively impairs insulin gene expression to result in insulin deficiency and diabetes. Selective dysregulation of gene expression in triplet repeat disorders provides a mechanism for pleiotropic cellular dysfunction that restricts the toxicity of ubiquitously expressed proteins to highly specialized subpopulations of cells.
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PMID:Huntington's disease of the endocrine pancreas: insulin deficiency and diabetes mellitus due to impaired insulin gene expression. 1258 50

Significant numerical and spatial changes in 5-HT i.r. cells, CCK i.r. I-cells, glucagon and glicentin i.r. I-cells, somatostatin i.r. D-cells and neurotensin i.r. N-cells occur after a 98% myenteric ablation in the rat. Signal transduction from G-protein-coupled crypt cell receptors (m2, m3; VCAP1 and 2, CAP1; Y2, Y5, Y4) stimulates a cAMP-responsive transcription machinery in which phosphorylation of the cAMP-responsive elements (e.g. CREB) is the first step in initiation of transcription. A DNA pre-initiation complex (PIC), consisting of DNA transcription activators, general activators (TFIID, IIA, IIB, IIF, IIE, II-I and IIH), at least 14 different TAFIIs and CBP/300 coactivators which contain multiple enzymatic activities, associated with the central TBP (TATA-binding protein), which together bind to the RNA-polymerase II holoenzyme disrupts chromatin blockade over the promoter with or without the intervention of activated chromatin remodeling factors. CBP/p300 contains several highly conserved domains e.g., KIX, whose methylation by CARM-1 represses CREB transcription activation, but the bromo-binding domain of CBP increases CREB transcription. A similar positive/negative switch occurs in the regulation of gastrointestinal hormones by transcription factors, from Myc/Max to Mad/Max + corepressor mSin3A, during terminal differentiation of the cell. From these observations we conclude that the primary targets for neural signals are factors of the basal DNA transcriptional apparatus, whose promoter factors then activate chromatin induction, which facilitates transcription positively or negatively.
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PMID:The influence of neural signal transduction on EEC gene expression under consideration of chromatin, following myenteric ablation (review). 1537 74

Recent studies indicate that the location of neurogenesis within the medial ganglionic eminence (MGE) critically influences the fate determination of cortical interneuron subgroups, with parvalbumin (Pv) interneurons originating from subventricular zone divisions and somatostatin (Sst) interneurons primarily arising from apical divisions. The aPKC-CBP and Notch signaling pathways regulate the transition from apical to basal progenitor and their differentiation into post-mitotic neurons. We find that aPKC inhibition enhances intermediate neurogenesis from stem cell-derived MGE progenitors, resulting in a markedly increased ratio of Pv- to Sst-expressing interneurons. Conversely, inhibition of Notch signaling enriches for Sst subtypes at the expense of Pv fates. These findings confirm that the mode of neurogenesis influences the fate of MGE-derived interneurons and provide a means of further enrichment for the generation of specific interneuron subgroups from pluripotent stem cells.
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PMID:Atypical PKC and Notch Inhibition Differentially Modulate Cortical Interneuron Subclass Fate from Embryonic Stem Cells. 2841 85