TY - JOUR
T1 - The tumor suppressor protein HBP1 is a novel c-Myc-binding protein that negatively regulates c-Myc transcriptional activity
AU - Escamilla-Powers, Julienne R.
AU - Daniel, Colin J.
AU - Farrell, Amy
AU - Taylor, Karyn
AU - Zhang, Xiaoli
AU - Byers, Sarah
AU - Sears, Rosalie
PY - 2010/2/12
Y1 - 2010/2/12
N2 - c-Myc is an important transcription factor that regulates cellular proliferation, cell growth, and differentiation.Anumber of transcriptional co-factors for c-Myc have been described that have binding sites within highly conserved regions of the c-Myc transactivational domain (TAD). Given the importance of the c-Myc TAD, we set out to identify new proteins that interact with this region using a yeast two-hybrid assay. HBP1 was identified in our screen as a protein that interacts with full-length c-Myc but not a c-Myc mutant lacking the TAD. HBP1 is a transcriptional repressor and has been shown to negatively regulate the cell cycle. A correlation between HBP1 under-expression and breast cancer relapse has been described, suggesting that HBP1 may be an important tumor suppressor protein. We have found that HBP1 binds c-Myc in cells, and expression of HBP1 inhibits c-Myc transactivational activity at least partly by preventing c-Myc binding to target gene promoters. c-Myc binds to theCterminus of HBP1, a region lost in some breast tumors, and some HBP1 mutants found in breast cancer weakly interact with and/or no longer negatively regulate c-Myc. This work adds to our understanding of c-Myc regulation and mechanisms of tumor suppression by HBP1.
AB - c-Myc is an important transcription factor that regulates cellular proliferation, cell growth, and differentiation.Anumber of transcriptional co-factors for c-Myc have been described that have binding sites within highly conserved regions of the c-Myc transactivational domain (TAD). Given the importance of the c-Myc TAD, we set out to identify new proteins that interact with this region using a yeast two-hybrid assay. HBP1 was identified in our screen as a protein that interacts with full-length c-Myc but not a c-Myc mutant lacking the TAD. HBP1 is a transcriptional repressor and has been shown to negatively regulate the cell cycle. A correlation between HBP1 under-expression and breast cancer relapse has been described, suggesting that HBP1 may be an important tumor suppressor protein. We have found that HBP1 binds c-Myc in cells, and expression of HBP1 inhibits c-Myc transactivational activity at least partly by preventing c-Myc binding to target gene promoters. c-Myc binds to theCterminus of HBP1, a region lost in some breast tumors, and some HBP1 mutants found in breast cancer weakly interact with and/or no longer negatively regulate c-Myc. This work adds to our understanding of c-Myc regulation and mechanisms of tumor suppression by HBP1.
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U2 - 10.1074/jbc.M109.074856
DO - 10.1074/jbc.M109.074856
M3 - Article
C2 - 20008325
AN - SCOPUS:77951184032
SN - 0021-9258
VL - 285
SP - 4847
EP - 4858
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 7
ER -