The tumor suppressor protein HBP1 is a novel c-Myc-binding protein that negatively regulates c-Myc transcriptional activity

Julienne R. Escamilla-Powers, Colin J. Daniel, Amy Farrell, Karyn Taylor, Xiaoli Zhang, Sarah Byers, Rosalie Sears

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4847-4858
Number of pages12
JournalJournal of Biological Chemistry
Volume285
Issue number7
DOIs
StatePublished - Feb 12 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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