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

J Biol Chem. 2002 Apr 12;277(15):12622-31. doi: 10.1074/jbc.M110568200. Epub 2002 Jan 25.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport*
  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • COS Cells
  • Cell Division / physiology*
  • Cloning, Molecular
  • DNA Primers
  • DNA, Complementary
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / physiology*
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • Molecular Sequence Data
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Proteins / genetics
  • Proteins / physiology*
  • Sequence Homology, Amino Acid
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins
  • ras GTPase-Activating Proteins*

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Apoptosis Regulatory Proteins
  • DAB2 protein, human
  • DAB2IP protein, human
  • DNA Primers
  • DNA, Complementary
  • GTPase-Activating Proteins
  • Proteins
  • Tumor Suppressor Proteins
  • ras GTPase-Activating Proteins

Associated data

  • GENBANK/AF236130