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.
Copyright policy )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.
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 University of Texas Southwestern Medical Center United States
Male, DNA, Complementary, Base Sequence, Sequence Homology, Amino Acid, GTPase-Activating Proteins, Molecular Sequence Data, Prostatic Neoplasms, Proteins, Adaptor Proteins, Vesicular Transport, COS Cells, Tumor Cells, Cultured, Animals, Humans, Genes, Tumor Suppressor, Amino Acid Sequence, Cloning, Molecular, Apoptosis Regulatory Proteins, Cell Division, Adaptor Proteins, Signal Transducing, DNA Primers
Male, DNA, Complementary, Base Sequence, Sequence Homology, Amino Acid, GTPase-Activating Proteins, Molecular Sequence Data, Prostatic Neoplasms, Proteins, Adaptor Proteins, Vesicular Transport, COS Cells, Tumor Cells, Cultured, Animals, Humans, Genes, Tumor Suppressor, Amino Acid Sequence, Cloning, Molecular, Apoptosis Regulatory Proteins, Cell Division, Adaptor Proteins, Signal Transducing, DNA Primers
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