Akt : A Double-Edged Sword in Cell Proliferation and Genome Stability
Joint Authors
Gillespie, David A.
Xu, Naihan
Zhang, Yaou
Lao, Yuanzhi
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-03-15
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
The Akt family of serine/threonine protein kinases are key regulators of multiple aspects of cell behaviour, including proliferation, survival, metabolism, and tumorigenesis.
Growth-factor-activated Akt signalling promotes progression through normal, unperturbed cell cycles by acting on diverse downstream factors involved in controlling the G1/S and G2/M transitions.
Remarkably, several recent studies have also implicated Akt in modulating DNA damage responses and genome stability.
High Akt activity can suppress ATR/Chk1 signalling and homologous recombination repair (HRR) via direct phosphorylation of Chk1 or TopBP1 or, indirectly, by inhibiting recruitment of double-strand break (DSB) resection factors, such as RPA, Brca1, and Rad51, to sites of damage.
Loss of checkpoint and/or HRR proficiency is therefore a potential cause of genomic instability in tumor cells with high Akt.
Conversely, Akt is activated by DNA double-strand breaks (DSBs) in a DNA-PK- or ATM/ATR-dependent manner and in some circumstances can contribute to radioresistance by stimulating DNA repair by nonhomologous end joining (NHEJ).
Akt therefore modifies both the response to and repair of genotoxic damage in complex ways that are likely to have important consequences for the therapy of tumors with deregulation of the PI3K-Akt-PTEN pathway.
American Psychological Association (APA)
Xu, Naihan& Lao, Yuanzhi& Zhang, Yaou& Gillespie, David A.. 2012. Akt : A Double-Edged Sword in Cell Proliferation and Genome Stability. Journal of Oncology،Vol. 2012, no. 2012, pp.1-15.
https://search.emarefa.net/detail/BIM-510885
Modern Language Association (MLA)
Xu, Naihan…[et al.]. Akt : A Double-Edged Sword in Cell Proliferation and Genome Stability. Journal of Oncology No. 2012 (2012), pp.1-15.
https://search.emarefa.net/detail/BIM-510885
American Medical Association (AMA)
Xu, Naihan& Lao, Yuanzhi& Zhang, Yaou& Gillespie, David A.. Akt : A Double-Edged Sword in Cell Proliferation and Genome Stability. Journal of Oncology. 2012. Vol. 2012, no. 2012, pp.1-15.
https://search.emarefa.net/detail/BIM-510885
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-510885