Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment

BMC Molecular Biology

Samit Chattopadhyay²  Pradeep Parab²  Sreenath Kadreppa²  Taronish Dubash²  Pavithra Lakshminarsimhan Chavali²  Varsheish Raina²  Sandeep Singh¹ 

[1] Sandeep Singh, Assistant Professor, Centre for Human Genetics, School of Health Sciences, Central University of Punjab, Bathinda, 151001, India;Samit Chattopadhyay, PhD, Scientist-G, National Centre for Cell Sciences, Pune, 411007, India

关键词: Streptozotocin;    p53;    GAD65;    Diabetes;    SMAR1;   

Others  :  1091577
DOI  :  10.1186/1471-2199-13-28

 received in 2011-11-15, accepted in 2012-09-07,  发布年份 2012

【 摘 要 】

Background

GAD65 (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.

Results

The 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.

Conclusion

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

【 授权许可】

   
2012 Singh et al.; licensee BioMed Central Ltd.

【 图 表 】

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