Characterization of human Gadd45, a p53-regulated protein.

Published

Journal Article

GADD45 (growth arrest and DNA damage) is a DNA-damage-inducible gene regulated in part by the tumor suppressor p53. A role in negative growth control has recently been suggested based on significant (more than 75%) reduction of colony formation following over expression of Gadd45. To better understand the role of Gadd45, we have developed specific rabbit and murine antibodies raised against the human recombinant protein. Using these antibodies, we have found that in ML-1 cells Gadd45 is predominantly a nuclear protein. MyD118, a protein induced by terminal differentiation sharing 57% homology with Gadd45, does not cross-react with any of the antibodies produced. As expected, the induction of Gadd45 protein by ionizing radiation (IR) was also found to be dependent on a wild type p53 phenotype. Interestingly, WI-L2-NS, a human lymphoid cell line, showed very high basal levels of Gadd45 mRNA and protein in addition to a high constitutive level of a mutated p53 protein. In this cell line, the high levels of GADD45 did not inhibit cellular growth in spite of the fact that no mutations were found in GADD45 sequence. These results indicate that some cell line(s) can tolerate high levels of Gadd45 and abrogate its growth suppression function.

Full Text

Duke Authors

Cited Authors

  • Carrier, F; Smith, ML; Bae, I; Kilpatrick, KE; Lansing, TJ; Chen, CY; Engelstein, M; Friend, SH; Henner, WD; Gilmer, TM

Published Date

  • December 23, 1994

Published In

Volume / Issue

  • 269 / 51

Start / End Page

  • 32672 - 32677

PubMed ID

  • 7798274

Pubmed Central ID

  • 7798274

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng

Conference Location

  • United States