Heat-shock protein 70 binds to a novel sequence in 5' UTR of tumor suppressor SMAR1 and regulates its mRNA stability upon Prostaglandin A2 treatment.
Here, we report Prostaglandin A2 (PGA2) induced binding of HSP70 to a novel site on phi1 SMAR1 5' UTR which stabilizes the wild type transcript and leads to subsequent increase in SMAR1 protein levels. SMAR1 mediated cell cycle arrest is perturbed in PGA2-treated cells when HSP70 is knocked-down. Contrarily HSP70, unlike SMAR1, is overexpressed in breast cancers. We demonstrate that this is because of the inability of HSP70 to bind to the phi17 SMAR1 UTR variant which is the predominant form in breast cancers.
National Centre for Cell Science, Pune University Campus, Ganeshkhind, Pune, India.
Lakshminarasimhan
L
Pavithra
Kadreppa
K
Sreenath
Sandeep
S
Singh
Samit
S
Chattopadhyay
D020121:5' Untranslated Regions; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009698:Nucleoproteins / Q000378:metabolism; D011454:Prostaglandins A / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; C417914:BANP protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D009698:Nucleoproteins; D011454:Prostaglandins A; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C100008:prostaglandin A2