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J. Biol. Chem., Vol. 277, Issue 15, 12622-12631, April 12, 2002
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From the 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.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AF236130.
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*
,,,,
Department of Urology, University of Texas
Southwestern Medical Center at Dallas, Dallas, Texas 75390-9110 and the
¶ Department of GU Medical Oncology, University of Texas M.D.
Anderson Cancer Center, Houston, Texas 77030
*
This work was supported by NIDDK, National Institutes of
Health, Grant DK-47657, Department of Defense Grant PC970259 (to J. T. H.), and funding from Gillson Longenbaugh (to J. D. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: University of
Texas Southwestern Medical Center, Dept. of Urology, 5323 Harry Hines
Blvd., Dallas, TX 75390-9110. Tel.: 214-648-3988; Fax: 214-648-8786; E-mail: JT.Hsieh@UTSouthwestern.edu.
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