Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatmentReportar como inadecuado




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BMC Molecular Biology

, 13:28

Transcriptional control of gene expression

Abstract

BackgroundGAD65 Glutamic acid decarboxylase 65 KDa isoform is one of the most important auto-antigens involved in Type 1 diabetes induction. Although it serves as one of the first injury markers of β-islets, the mechanisms governing GAD65 expression remain poorly understood. Since the regulation of GAD65 is crucial for the proper functioning of insulin secreting cells, we investigated the stress induced regulation of GAD65 transcription.

ResultsThe present study shows that SMAR1 regulates GAD65 expression at the transcription level. Using a novel protein-DNA pull-down assay, we show that SMAR1 binding is very specific to GAD65 promoter but not to the other isoform, GAD67. We show that Streptozotocin STZ mediated DNA damage leads to upregulation of SMAR1 and p53 expression, resulting in elevated levels of GAD65, in both cell lines as well as mouse β-islets. SMAR1 and p53 act synergistically to up-regulate GAD65 expression upon STZ treatment.

ConclusionWe propose a novel mechanism of GAD65 regulation by synergistic activities of SMAR1 and p53.

KeywordsSMAR1 Diabetes GAD65 p53 Streptozotocin Electronic supplementary materialThe online version of this article doi:10.1186-1471-2199-13-28 contains supplementary material, which is available to authorized users.

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Autor: Sandeep Singh - Varsheish Raina - Pavithra Lakshminarsimhan Chavali - Taronish Dubash - Sreenath Kadreppa - Pradeep Parab -

Fuente: https://link.springer.com/







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