ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress

Journal Article · Fri Aug 26 00:00:00 EDT 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.06.097· OSTI ID:20710925

Pauklin, Siim ^[1]; Kristjuhan, Arnold ^[1]; Maimets, Toivo ^[1]; Jaks, Viljar ^[1]

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1. Department of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, 23 Riia Street, Tartu 51010 (Estonia)

Induction of apoptosis is pivotal for eliminating cells with damaged DNA or deregulated proliferation. We show that tumor suppressor ARF and ATM/ATR kinase pathways cooperate in the induction of apoptosis in response to elevated expression of c-myc, {beta}-catenin or human papilloma virus E7 oncogenes. Overexpression of oncogenes leads to the formation of phosphorylated H2AX foci, induction of Rad51 protein levels and ATM/ATR-dependent phosphorylation of p53. Inhibition of ATM/ATR kinases abolishes both induction of Rad51 and phosphorylation of p53, and remarkably reduces the level of apoptosis induced by co-expression of oncogenes and ARF. However, the induction of apoptosis is downregulated in p53-/- cells and does not depend on activities of ATM/ATR kinases, indicating that efficient induction of apoptosis by oncogene activation depends on coordinated action of ARF and ATM/ATR pathways in the regulation of p53.

• OSTI ID: 20710925
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 334, Issue 2; Other Information: DOI: 10.1016/j.bbrc.2005.06.097; PII: S0006-291X(05)01318-5; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
ARGON FLUORIDES
CELL PROLIFERATION
DNA
DNA REPAIR
GENE REGULATION
NEOPLASMS
ONCOGENES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
STRAND BREAKS
VIRUSES