The mechanism of growth-inhibitory effect of DOC-2/DAB2 in prostate cancer. Characterization of a novel GTPase-activating protein associated with N-terminal domain of DOC-2/DAB2

Zhi Wang, Ching Ping Tseng, Rey Chen Pong, Hong Chen, John D. McConnell, Nora Navone, Jer Tsong Hsieh

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

DOC-2/DAB2 is a member of the disable gene family with tumor-inhibitory activity. Its down-regulation is associated with several neoplasms, and serine phosphorylation of its N terminus modulates DOC-2/DAB2's inhibitory effect on AP-1 transcriptional activity. We describe the cloning of DIP1/2, a novel gene that interacts with the N-terminal domain of DOC-2/DAB2. DIP1/2 is a novel GTPase-activating protein containing a Ras GTPase-activating protein homology domain (N terminus) and two other unique domains (i.e. 10 proline repeats and leucine zipper). Interaction between DOC-2/DAB2 and DIP1/2 is detected in normal tissues such as the brain and prostate. Altered expression of these two proteins is often detected in prostate cancer cells. Indeed, the presence of DIP1/2 effectively blocks mitogen-induced gene expression and inhibits the growth of prostate cancer. Thus, DOC-2/DAB2 and DIP1/2 appear to represent a unique negative regulatory complex that maintains cell homeostasis.

Original languageEnglish (US)
Pages (from-to)12622-12631
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number15
DOIs
StatePublished - Apr 12 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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