title: Regulation of GAD65 expression by SMAR1 and p53 upon Streptozotocin treatment.
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 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.
  
  
  CONCLUSIONS
  We propose a novel mechanism of GAD65 regulation by synergistic activities of SMAR1 and p53.
authors.affiliation: Centre for Human Genetics, School of Health Sciences, Central University of Punjab, Bathinda 151001, India. sandeepsingh82@gmail.com
authors.forename: Sandeep
authors.initials: S
authors.lastname: Singh
authors.forename: Varsheish
authors.initials: V
authors.lastname: Raina
authors.forename: Pavithra Lakshminarsimhan
authors.initials: PL
authors.lastname: Chavali
authors.forename: Taronish
authors.initials: T
authors.lastname: Dubash
authors.forename: Sreenath
authors.initials: S
authors.lastname: Kadreppa
authors.forename: Pradeep
authors.initials: P
authors.lastname: Parab
authors.forename: Samit
authors.initials: S
authors.lastname: Chattopadhyay
mesh_terms: D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D008156:Luciferases; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000378:metabolism; D016415:Sequence Alignment; D013311:Streptozocin / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C485952:Banp protein, mouse; D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53; D013311:Streptozocin; D004247:DNA; D008156:Luciferases; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2