AUTHOR=Zhou Guisheng , Sinnett-Smith Jim , Liu Shi-He , Yu Juehua , Wu James , Sanchez Robbi , Pandol Stephen J. , Abrol Ravinder , Nemunaitis John , Rozengurt Enrique , Brunicardi F. Charles TITLE=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 JOURNAL=Frontiers in Physiology VOLUME=5 YEAR=2014 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2014.00226 DOI=10.3389/fphys.2014.00226 ISSN=1664-042X ABSTRACT=

Somatostatin (SST) is a regulatory peptide and acts as an endogenous inhibitory regulator of the secretory and proliferative responses of target cells. SST’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, β cell differentiation, maintenance of normal β 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.