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 Citations (Scopus)

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

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Proto-Oncogene Proteins c-myc
Tumor Suppressor Proteins
Tumors
Carrier Proteins
Breast Neoplasms
Cell growth
Yeast
Assays
Two-Hybrid System Techniques
Proteins
Transcription Factors
Genes
Binding Sites
Cells
Cell Differentiation
Cell Cycle
Cell Proliferation
Recurrence
Growth
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

The tumor suppressor protein HBP1 is a novel c-Myc-binding protein that negatively regulates c-Myc transcriptional activity. / Escamilla-Powers, Julienne R.; Daniel, Colin J.; Farrell, Amy; Taylor, Karyn; Zhang, Xiaoli; Byers, Sarah; Sears, Rosalie.

In: Journal of Biological Chemistry, Vol. 285, No. 7, 12.02.2010, p. 4847-4858.

Research output: Contribution to journalArticle

Escamilla-Powers, Julienne R. ; Daniel, Colin J. ; Farrell, Amy ; Taylor, Karyn ; Zhang, Xiaoli ; Byers, Sarah ; Sears, Rosalie. / The tumor suppressor protein HBP1 is a novel c-Myc-binding protein that negatively regulates c-Myc transcriptional activity. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 7. pp. 4847-4858.
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