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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport*
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Amino Acid Sequence
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Animals
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Apoptosis Regulatory Proteins
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Base Sequence
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COS Cells
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Cell Division / physiology*
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Cloning, Molecular
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DNA Primers
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DNA, Complementary
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GTPase-Activating Proteins / chemistry
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GTPase-Activating Proteins / physiology*
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Genes, Tumor Suppressor
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Humans
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Male
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Molecular Sequence Data
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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Proteins / genetics
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Proteins / physiology*
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Sequence Homology, Amino Acid
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Tumor Cells, Cultured
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Tumor Suppressor Proteins
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ras GTPase-Activating Proteins*
Substances
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Adaptor Proteins, Signal Transducing
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Adaptor Proteins, Vesicular Transport
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Apoptosis Regulatory Proteins
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DAB2 protein, human
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DAB2IP protein, human
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DNA Primers
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DNA, Complementary
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GTPase-Activating Proteins
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Proteins
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Tumor Suppressor Proteins
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ras GTPase-Activating Proteins