Title: p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2
Authors: Aliouat-Denis, Cécile-Marie ×
Dendouga, Najoua
Van den Wyngaert, Ilse
Goehlmann, Hinrich
Steller, Ulf
van de Weyer, Inez
Van Slycken, Nele
Andries, Luc
Kass, Stefan
Luyten, Walter
Janicot, Michel
Vialard, Jorge E #
Issue Date: Nov-2005
Series Title: Molecular Cancer Research vol:3 issue:11 pages:627-34
Abstract: The Chk2 kinase is a tumor suppressor and key component of the DNA damage checkpoint response that encompasses cell cycle arrest, apoptosis, and DNA repair. It has also been shown to have a role in replicative senescence resulting from dysfunctional telomeres. Some of these functions are at least partially exerted through activation of the p53 transcription factor. High-level expression of virally transduced Chk2 in A549 human lung carcinoma cells led to arrested proliferation, apoptosis, and senescence. These were accompanied by various molecular events, including p21(Waf1/Cip1) (p21) transcriptional induction, consistent with p53 activation. However, Chk2-dependent senescence and p21 transcriptional induction also occurred in p53-defective SK-BR-3 (breast carcinoma) and HaCaT (immortalized keratinocyte) cells. Small interfering RNA-mediated knockdown of p21 in p53-defective cells expressing Chk2 resulted in a decrease in senescent cells. These results revealed a p53-independent role for Chk2 in p21 induction and senescence that may contribute to tumor suppression and genotoxic treatment outcome.
ISSN: 1541-7786
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Section Woman - Miscellaneous (-)
Department of Pharmaceutical & Pharmacological Sciences - miscellaneous
× corresponding author
# (joint) last author

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