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Rapamycin and p53 act on different pathways to induce G1 arrest in mammalian cells.

Publication ,  Journal Article
Metcalfe, SM; Canman, CE; Milner, J; Morris, RE; Goldman, S; Kastan, MB
Published in: Oncogene
October 2, 1997

Certain growth regulatory kinases contain a common domain related to the phospho-inositol 3 (PI-3) kinase catalytic site. These include the ATM gene product, DNA-PKcs, and the target of rapamycin (TOR in yeast; and FRAP in mammalian cells). Rapamycin inhibits growth factor signalling and induces G1 arrest in many cell types. Some growth regulatory PI-3 kinases appear functionally linked to p53 and we have explored potential links between cellular effects induced by rapamycin and p53. In p53 null cells rapamycin inhibited cell cycling but did not induce G1 arrest. In cells which showed selective G1 arrest in response to rapamycin, rapamycin had no effect on basal levels of p53 protein. Similarly p21(WAF1) protein was not induced by rapamycin. The kinetics of the cellular p53/p21(WAF1) response to ionising radiation was unaffected by rapamycin; and the ability of growth factor to protect against p53-mediated apoptosis in response to DNA damage was also unaffected by rapamycin. The ATM gene is mutated in the cancer susceptibility syndrome ataxia telangiectasia (AT) but such mutant cells showed a similar sensitivity to rapamycin compared to their normal counterparts. RKO cell lines of common genetic background, but with different levels of functional p53 protein, also responded similarly to rapamycin. Thus, although rapamycin and p53 are each able to induce G1 arrest, they appear to act through independent growth regulatory pathways.

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Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

October 2, 1997

Volume

15

Issue

14

Start / End Page

1635 / 1642

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • TOR Serine-Threonine Kinases
  • Sirolimus
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Proteins
  • Protein Serine-Threonine Kinases
  • Polyenes
 

Citation

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Metcalfe, S. M., Canman, C. E., Milner, J., Morris, R. E., Goldman, S., & Kastan, M. B. (1997). Rapamycin and p53 act on different pathways to induce G1 arrest in mammalian cells. Oncogene, 15(14), 1635–1642. https://doi.org/10.1038/sj.onc.1201341
Metcalfe, S. M., C. E. Canman, J. Milner, R. E. Morris, S. Goldman, and M. B. Kastan. “Rapamycin and p53 act on different pathways to induce G1 arrest in mammalian cells.Oncogene 15, no. 14 (October 2, 1997): 1635–42. https://doi.org/10.1038/sj.onc.1201341.
Metcalfe SM, Canman CE, Milner J, Morris RE, Goldman S, Kastan MB. Rapamycin and p53 act on different pathways to induce G1 arrest in mammalian cells. Oncogene. 1997 Oct 2;15(14):1635–42.
Metcalfe, S. M., et al. “Rapamycin and p53 act on different pathways to induce G1 arrest in mammalian cells.Oncogene, vol. 15, no. 14, Oct. 1997, pp. 1635–42. Pubmed, doi:10.1038/sj.onc.1201341.
Metcalfe SM, Canman CE, Milner J, Morris RE, Goldman S, Kastan MB. Rapamycin and p53 act on different pathways to induce G1 arrest in mammalian cells. Oncogene. 1997 Oct 2;15(14):1635–1642.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

October 2, 1997

Volume

15

Issue

14

Start / End Page

1635 / 1642

Location

England

Related Subject Headings

  • Tumor Suppressor Proteins
  • Tumor Suppressor Protein p53
  • Tumor Cells, Cultured
  • TOR Serine-Threonine Kinases
  • Sirolimus
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins
  • Proteins
  • Protein Serine-Threonine Kinases
  • Polyenes