A PDX1-ATF transcriptional complex governs β cell survival during stress

Molecular Metabolism
Christine A JulianaDoris A Stoffers

Abstract

Loss of insulin secretion due to failure or death of the insulin secreting β cells is the central cause of diabetes. The cellular response to stress (endoplasmic reticulum (ER), oxidative, inflammatory) is essential to sustain normal β cell function and survival. Pancreatic and duodenal homeobox 1 (PDX1), Activating transcription factor 4 (ATF4), and Activating transcription factor 5 (ATF5) are transcription factors implicated in β cell survival and susceptibility to stress. Our goal was to determine if a PDX1-ATF transcriptional complex or complexes regulate β cell survival in response to stress and to identify direct transcriptional targets. Pdx1, Atf4 and Atf5 were silenced by viral delivery of gRNAs or shRNAs to Min6 insulinoma cells or primary murine islets. Gene expression was assessed by qPCR, RNAseq analysis, and Western blot analysis. Chromatin enrichment was measured in the Min6 β cell line and primary isolated mouse islets by ChIPseq and ChIP PCR. Immunoprecipitation was used to assess interactions among transcription factors in Min6 cells and isolated mouse islets. Activation of caspase 3 by immunoblotting or by irreversible binding to a fluorescent inhibitor was taken as an indication of commitment to an apoptotic ...Continue Reading

Citations

Oct 22, 2020·Journal of Immunology Research·Xiaofeng YeLu-Lu Chen
Dec 24, 2020·Science Advances·Bingyuan YangWenbiao Chen
Apr 23, 2021·Scientific Reports·Gabriela Alves BronczekJosé Maria Costa-Júnior
May 26, 2021·Trends in Endocrinology and Metabolism : TEM·Matthew Wortham, Maike Sander
Jun 25, 2021·Nature Reviews. Endocrinology·Jing YongRandal J Kaufman

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
PCR
RNAseq
ChIPseq
co-immunoprecipitation

Software Mentioned

SuperExactTest R package
human LiftOver
UCSC

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Adenoma, Islet Cell

Islet Cell Adenoma arises in the islet cells, which are insulin producing cells of the pancreas. These tumors can be either malignant or benign. Discover the latest research on Islet Cell Adenoma here.

Antidiabetic Cellular Plasticity

This feed focuses on mechanisms that underlie cellular plasticity as a treatment for diabetes and other degenerative diseases.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Christine A JulianaDoris A Stoffers
Proceedings of the National Academy of Sciences of the United States of America
Mira M SachdevaDoris A Stoffers
Molecular Endocrinology
Cynthia KhooDoris A Stoffers
© 2022 Meta ULC. All rights reserved