PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes

Oncogene. 1999 Jan 7;18(1):127-37. doi: 10.1038/sj.onc.1202274.

Abstract

Exposure of mammalian cells to hypoxia, radiation and certain chemotherapeutic agents promotes cell cycle arrest and/or apoptosis. Activation of p53 responsive genes is believed to play an important role in mediating such responses. In this study we identified a novel gene, PA26, which maps to chromosome 6q21 and encodes at least three transcript isoforms, of which two are differentially induced by genotoxic stress (UV, gamma-irradiation and cytotoxic drugs) in a p53-dependent manner. A functional p53-responsive element was identified in the second intron of the PA26 gene, in consistance with a mechanism of transcriptional induction of the PA26 gene by p53. No clues to its functions were revealed by sequence analysis, although pronounced negative regulation by serum factors argues for a potential role of PA26 in growth regulation. Immunological analysis suggests that PA26 protein(s) is localized to the cell nucleus. Our results suggest that the PA26 gene is a novel p53 target gene with properties common to the GADD family of growth arrest and DNA damage-inducible stress-response genes, and, thus, a potential novel regulator of cellular growth.

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Division
  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6*
  • Cloning, Molecular
  • DNA Damage*
  • DNA, Complementary
  • Gene Expression Regulation
  • Heat-Shock Proteins*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Molecular Sequence Data
  • Proteins / genetics*
  • Response Elements
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • DNA, Complementary
  • GADD45 protein
  • Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SESN1 protein, human
  • Tumor Suppressor Protein p53

Associated data

  • GENBANK/AF033120
  • GENBANK/AF033121
  • GENBANK/AF033122