%0 Journal Article
%T Down-regulation of pancreatic and duodenal homeobox-1 by somatostatin receptor subtype 5: a novel mechanism for inhibition of cellular proliferation and insulin secretion by somatostatin
%A Charles Brunicardi
%A Guisheng Zhou
%A James Wu
%A Stephen J. Pandol
%A Ravinder Abrol
%A Enrique Rozengurt
%J Frontiers in Physiology
%D 2014
%I Frontiers Media
%R 10.3389/fphys.2014.00226
%X Somatostatin is a regulatory peptide and acts as an endogenous inhibitory regulator of the secretory and proliferative responses of target cells. Somatostatin¡¯s actions are mediated by a family of seven transmembrane domain G protein-coupled receptors that comprise five distinct subtypes (SSTR1-5). SSTR5 is one of the major SSTRs in the islets of Langerhans. Homeodomain-containing transcription factor pancreatic and duodenal homeobox-1 (PDX-1) is essential for pancreatic development, ¦Â cell differentiation, maintenance of normal ¦Â cell functions in adults and tumorigenesis. Recent studies show that SSTR5 acts as a negative regulator for PDX-1 expression and that SSTR5 mediates somatostatin¡¯s inhibitory effect on cell proliferation and insulin expression/excretion through down-regulating PDX-1 expression. SSTR5 exerts its inhibitory effect on PDX-1 expression at both the transcriptional level by down-regulating PDX-1 mRNA and the post-translational level by enhancing PDX-1 ubiquitination. Identification of PDX-1 as a transcriptional target for SSTR5 may help in guiding the choice of therapeutic cancer treatments.
%K G protein-coupled receptors
%K pancreatic and duodenal homeobox-1
%K Single nucleotide polymorphisms
%K Somatostatin
%K somatostatin receptor
%U http://www.frontiersin.org/Journal/10.3389/fphys.2014.00226/abstract