Abstract
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.
Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
5' Untranslated Regions*
-
Base Sequence
-
Breast Neoplasms / genetics
-
Breast Neoplasms / metabolism
-
Breast Neoplasms / pathology
-
Cell Cycle Proteins / genetics*
-
Cell Cycle Proteins / metabolism
-
DNA-Binding Proteins / genetics*
-
DNA-Binding Proteins / metabolism
-
Gene Expression Regulation
-
HSP70 Heat-Shock Proteins / metabolism*
-
Humans
-
Macromolecular Substances / metabolism
-
Models, Biological
-
Nuclear Proteins / genetics*
-
Nuclear Proteins / metabolism
-
Nucleic Acid Conformation
-
Nucleoproteins / metabolism
-
Prostaglandins A / pharmacology*
-
Protein Binding / drug effects
-
Protein Binding / physiology
-
RNA Stability / drug effects*
-
RNA, Messenger / chemistry
-
RNA, Messenger / drug effects
-
RNA, Messenger / metabolism
-
Tumor Cells, Cultured
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism
Substances
-
5' Untranslated Regions
-
BANP protein, human
-
Cell Cycle Proteins
-
DNA-Binding Proteins
-
HSP70 Heat-Shock Proteins
-
Macromolecular Substances
-
Nuclear Proteins
-
Nucleoproteins
-
Prostaglandins A
-
RNA, Messenger
-
Tumor Suppressor Proteins
-
prostaglandin A2