Cloning and characterization of a p53 and DNA damage down-regulated gene PIQ that codes for a novel calmodulin-binding IQ motif protein and is up-regulated in gastrointestinal cancers

Cancer Res. 2005 Dec 1;65(23):10725-33. doi: 10.1158/0008-5472.CAN-05-1132.

Abstract

We have identified a p53 and DNA damage-regulated gene that encodes a novel IQ motif protein, which we have named p53 and DNA damage-regulated IQ motif protein (PIQ). PIQ has two isoforms, long (PIQ-L) and short (PIQ-S), and both bind to calmodulin in the presence and absence of calcium. PIQ expression is down-regulated by p53 and DNA damage-inducing agents, whereas PIQ itself represses the expression of p53 up-regulated modulator of apoptosis that is a key mediator of p53-induced apoptosis. Thus, PIQ is a novel protein that may function to bridge a crosstalk between p53 and calmodulin-regulated cellular processes. We further show that PIQ expression is up-regulated in a number of primary colorectal and gastric tumors when compared with matching normal tissues, suggesting that PIQ may be involved in tumorigenesis and could serve as a valuable diagnostic/prognostic marker for gastrointestinal tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / genetics
  • Calmodulin / metabolism
  • Calmodulin-Binding Proteins / genetics*
  • Calmodulin-Binding Proteins / metabolism
  • Cell Line, Tumor
  • Cloning, Molecular
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Consensus Sequence
  • DNA Damage*
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Sequence Alignment
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Transfection
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Apoptosis Regulatory Proteins
  • BBC3 protein, human
  • Calmodulin
  • Calmodulin-Binding Proteins
  • IQCB1 protein, human
  • Proto-Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53