• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

c-Myc-regulated microRNAs modulate E2F1 expression.

MicroRNAs (miRNAs) are 21-23 nucleotide RNA molecules that regulate the stability or translational efficiency of target messenger RNAs. miRNAs have diverse functions, including the regulation of cellular differentiation, proliferation and apoptosis. Although strict tissue- and developmental-stage-specific expression is critical for appropriate miRNA function, mammalian transcription factors that regulate miRNAs have not yet been identified. The proto-oncogene c-MYC encodes a transcription factor that regulates cell proliferation, growth and apoptosis. Dysregulated expression or function of c-Myc is one of the most common abnormalities in human malignancy. Here we show that c-Myc activates expression of a cluster of six miRNAs on human chromosome 13. Chromatin immunoprecipation experiments show that c-Myc binds directly to this locus. The transcription factor E2F1 is an additional target of c-Myc that promotes cell cycle progression. We find that expression of E2F1 is negatively regulated by two miRNAs in this cluster, miR-17-5p and miR-20a. These findings expand the known classes of transcripts within the c-Myc target gene network, and reveal a mechanism through which c-Myc simultaneously activates E2F1 transcription and limits its translation, allowing a tightly controlled proliferative signal.

Pubmed ID: 15944709

Authors

  • O'Donnell KA
  • Wentzel EA
  • Zeller KI
  • Dang CV
  • Mendell JT

Journal

Nature

Publication Data

June 9, 2005

Associated Grants

None

Mesh Terms

  • Animals
  • Cell Cycle Proteins
  • Cell Line
  • Chromatin Immunoprecipitation
  • Chromosomes, Human, Pair 13
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Gene Expression Regulation
  • Humans
  • MicroRNAs
  • Protein Binding
  • Proto-Oncogene Proteins c-myc
  • Rats
  • Transcription Factors