Skip to main content

Similarity of the DNA-damage responsiveness and growth-suppressive properties of waf1/cip1 and gadd45.

Publication ,  Journal Article
Zhan, Q; Eldeiry, W; Bae, I; Alamo, I; Kastan, M; Vogelstein, B; Fornace, A
Published in: Int J Oncol
May 1995

The cellular responses to genotoxic stress are complex involving both p53-dependent and independent mechanisms. In the case of the GADD genes, many stresses eliciting growth arrest have been shown to induce these genes in a coordinate fashion regardless of p53 status, while the ionizing radiation response (IR) of GADD45 has been found to be strictly p53-dependent. In the current study, the response of GADD45 was compared to the p53-regulated genes WAF1/CIP1 and MDM2 in a panel of human lines with known p53 status and also in mouse embryo fibroblasts where one or both alleles of p53 had been deleted. After IR, all 3 genes showed very similar transcriptional responses as measured by rapid increases in mRNA. in a p53-dependent manner. Like GADD45, the WAF1/CIP1 induction by IR can be enhanced by the radiosensitizer iododeoxyuridine, and provides further evidence that DNA strand breaks can act as a signal for activation of the p53 pathway. In addition, caffeine, which blocks IR cell-cycle checkpoint activation, reduced IR induction for both genes. Unlike the case for IR, only WAF1/CIP1 showed a consistent similarity to GADD45 to DNA base-damaging agents, where appreciable induction occurred in cells regardless of p53 status. The similarity between WAF1/CIP1 and GADD45 also extended to their growth suppressive properties, and a combination of expression vectors for these genes suppressed growth appreciably more than either alone. A reasonable interpretation of these results is that growth suppression after DNA damage by either p53-dependent or independent pathways is mediated by the combined action of multiple downstream effecters including WAF1/CIP1 and GADD45.

Duke Scholars

Published In

Int J Oncol

DOI

ISSN

1019-6439

Publication Date

May 1995

Volume

6

Issue

5

Start / End Page

937 / 946

Location

Greece

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhan, Q., Eldeiry, W., Bae, I., Alamo, I., Kastan, M., Vogelstein, B., & Fornace, A. (1995). Similarity of the DNA-damage responsiveness and growth-suppressive properties of waf1/cip1 and gadd45. Int J Oncol, 6(5), 937–946. https://doi.org/10.3892/ijo.6.5.937
Zhan, Q., W. Eldeiry, I. Bae, I. Alamo, M. Kastan, B. Vogelstein, and A. Fornace. “Similarity of the DNA-damage responsiveness and growth-suppressive properties of waf1/cip1 and gadd45.Int J Oncol 6, no. 5 (May 1995): 937–46. https://doi.org/10.3892/ijo.6.5.937.
Zhan Q, Eldeiry W, Bae I, Alamo I, Kastan M, Vogelstein B, et al. Similarity of the DNA-damage responsiveness and growth-suppressive properties of waf1/cip1 and gadd45. Int J Oncol. 1995 May;6(5):937–46.
Zhan, Q., et al. “Similarity of the DNA-damage responsiveness and growth-suppressive properties of waf1/cip1 and gadd45.Int J Oncol, vol. 6, no. 5, May 1995, pp. 937–46. Pubmed, doi:10.3892/ijo.6.5.937.
Zhan Q, Eldeiry W, Bae I, Alamo I, Kastan M, Vogelstein B, Fornace A. Similarity of the DNA-damage responsiveness and growth-suppressive properties of waf1/cip1 and gadd45. Int J Oncol. 1995 May;6(5):937–946.

Published In

Int J Oncol

DOI

ISSN

1019-6439

Publication Date

May 1995

Volume

6

Issue

5

Start / End Page

937 / 946

Location

Greece

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 3101 Biochemistry and cell biology
  • 1112 Oncology and Carcinogenesis