Inhibition of Smad antiproliferative function by CDK phosphorylation

Fang Liu, Isao Matsuura

Research output: Contribution to journalReview articlepeer-review

48 Scopus citations


Rb family members were the only demonstrated substrates of CDK4 until it was shown recently that Smad3, which plays a key role in mediating TGF-β antiproliferative responses, is phosphorylated by both CDK4 and CDK2 in vivo and in vitro. CDK phosphorylation of Smad3 inhibits its transcriptional activity and antiproliferative function. The Rb pathway is disrupted in almost all human cancers. Most cancers contain high levels of CDK activity due to frequent inactivation of the pi6 tumor suppressor or overexpression of cyclin Dl. Therefore, disruption of the Rb pathway not only inactivates Rb, but also likely diminishes Smad activity, which may contribute to tumorigenesis and resistance to the TGF-β growth-inhibitory effects in cancers. Although genetic mutation of Smad3 has not been reported, CDK phosphorylation of Smad3 may provide an epigenetic mechanism for inhibition of the tumor suppressive function of Smad3 during the early stages of tumorigenesis.

Original languageEnglish (US)
Pages (from-to)63-66
Number of pages4
JournalCell Cycle
Issue number1
StatePublished - Jan 2005

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


  • Cell cycle control
  • Cyclin-dependent kinases
  • Smad
  • TGF-β
  • Tumorigenesis


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