Sequence-specific DNA binding activity of RNA helicase A to the p16INK4a promoter

S. Myöhänen, S. B. Baylin

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


p16INK4a is frequently altered in human cancer, often through epigenetically mediated transcriptional silencing. However, little is known about the transcriptional regulation of this gene. To learn more about such control, we initiated studies of proteins that bind to the promoter in cancer cells that do, and do not, express the gene. We identify RNA helicase A (RHA) as a protein that binds much better to the p16INK4a promoter in the expressing cells. RHA has not previously been characterized to manifest sequence-specific DNA interaction but does so to the sequence 5′ CGG ACC GCG TGC GC 3′ in the p16INK4a promoter. The Drosophila homologue to RHA, maleless (Mle), functions in the fly for 2-fold activation of male X-chromosome genes. In our experimental setting, RHA induces a similar modest up-regulation of the p16INK4a promoter that is dependent upon its sequence-specific interaction. Mle colocalizes with hyperacetylated H4Ac16 on the X-chromosome and some autosomal loci. The decreased binding of RHA to p16INK4a in our cells, where the gene is transcriptionally inactive, is associated with decreased amounts of RHA that immunoprecipitate with acetylated lysine antibodies. Finally, we show RHA to be a cellular substrate for caspase-3, which decreases its sequence-specific binding to p16INK4a by cleavage of the N terminus. Thus, we have identified a new protein interaction with the p16INK4a promoter that involves an important protein for transcriptional modulation. This interaction is decreased in cancer cells, where this gene is aberrantly transcriptionally silent.

Original languageEnglish (US)
Pages (from-to)1634-1642
Number of pages9
JournalJournal of Biological Chemistry
Issue number2
StatePublished - Jan 12 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Sequence-specific DNA binding activity of RNA helicase A to the p16INK4a promoter'. Together they form a unique fingerprint.

Cite this