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
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.
Additional Information
© 2014 Zhou, Sinnett-Smith, Liu, Yu, Wu, Sanchez, Pandol, Abrol, Nemunaitis, Rozengurt and Brunicardi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 25 April 2014; Accepted: 31 May 2014; Published online: 25 June 2014. This work was supported by The Pilot and Feasibility Study Grant from the CURE: Digestive Disease Research Center (P30DK41301) (to Guisheng Zhou) and the National Institutes of Health (NIH) grants NIDDK R01-DK46441 and NCI R01-CA095731 and Ann and Jerry Moss Foundation (to F. Charles Brunicardi). Gratitude is extended to Katie Elsbury for her editorial assistance and Priscilla Massey and Jacqueline Ismen for their administrative assistance. Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Attached Files
Published - fphys-05-00226.pdf
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Additional details
- PMCID
- PMC4069483
- Eprint ID
- 47192
- Resolver ID
- CaltechAUTHORS:20140714-154111231
- P30DK41301
- CURE Digestive Disease Research Center
- NIDDK R01-DK46441
- NIH
- NCI R01-CA095731
- NIH
- Ann and Jerry Moss Foundation
- Created
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2014-07-15Created from EPrint's datestamp field
- Updated
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2021-11-10Created from EPrint's last_modified field