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Transcriptional Regulation of CRD-BP by c-myc: Implications for c-myc Functions

Felicite K Noubissi1, Mikhail A Nikiforov, Nancy Colburn

  • 1Department of Dermatology and Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.

Genes & Cancer
|July 23, 2011
PubMed

Insights

The coding region determinant binding protein (CRD-BP) is reactivated in cancer. This study identifies c-myc as a novel regulator that induces CRD-BP transcription, impacting cell growth and proliferation.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • RNA Regulation

Background:

  • The coding region determinant binding protein (CRD-BP) is a multifunctional RNA-binding protein crucial for embryonic development.
  • CRD-BP expression is typically low in adult tissues but reactivated and overexpressed in various cancers, correlating with aggressive disease.
  • CRD-BP regulates key genes, including oncogenes like c-myc, and its dysregulation contributes to cancer progression.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating CRD-BP expression.
  • To identify novel transcriptional regulators of CRD-BP.
  • To understand how c-myc influences CRD-BP expression and its downstream effects.

Main Methods:

  • Promoter binding assays to assess c-myc interaction with the CRD-BP promoter.
  • Transcriptional assays to measure c-myc-induced CRD-BP transcription.
  • Analysis of downstream targets and pathways affected by c-myc-mediated CRD-BP upregulation.

Main Results:

  • c-myc directly binds to the CRD-BP promoter region.
  • c-myc induces the transcription of CRD-BP.
  • Upregulation of CRD-BP by c-myc contributes to increased cell size, accelerated cell cycle progression, and enhanced translation regulation via modulation of β-TrCP1 and PDCD4.

Conclusions:

  • c-myc is identified as a novel transcriptional regulator of CRD-BP.
  • The c-myc/CRD-BP axis plays a significant role in promoting cancer-associated phenotypes.
  • Targeting this regulatory pathway could offer new therapeutic strategies for cancers with CRD-BP overexpression.

Keywords:
CRD-BPPDCD4c-mycprotein translationβ-TrCP1

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