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PMID:22978699
| Citation |
Singh, S, Raina, V, Lakshminarsimhan Chavali, P, Dubash, T, Kadreppa, S, Parab, P and Chattopadhyay, S (2012) Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment. BMC Mol. Biol. 13:28 |
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| Abstract |
ABSTRACT: 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 beta-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 beta-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. |
| Links |
PubMed Online version:10.1186/1471-2199-13-28 |
| Keywords |
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| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0045893: positive regulation of transcription, DNA-dependent |
ECO:0000315: |
P |
Figure 3a shows that over expression of SMAR1 upregulates GAD65. |
complete | ||||
|
involved_in |
GO:0045893: positive regulation of transcription, DNA-templated |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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