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

117 Citations (Scopus)

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

Fingerprint

GTPase-Activating Proteins
Prostatic Neoplasms
Genes
ras GTPase-Activating Proteins
Leucine Zippers
Phosphorylation
Cloning
Transcription Factor AP-1
Growth
Mitogens
Proline
Gene expression
Serine
Organism Cloning
Tumors
Prostate
Brain
Neoplasms
Homeostasis
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

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

In: Journal of Biological Chemistry, Vol. 277, No. 15, 12.04.2002, p. 12622-12631.

Research output: Contribution to journalArticle

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