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Sci. Signal., 22 January 2013
Vol. 6, Issue 259, p. ra5
Stalling the Death Warrant
The DNA damage response (DDR) involves an intricate network that regulates repair of the damage, cell cycle arrest, and apoptosis. In pluripotent embryonic stem (ES) cells, the DDR also regulates differentiation. With functional genomics, transcriptomics, and phosphoproteomics, Carreras Puigvert et al. investigated the DDR in ES cells treated with cisplatin, a DNA interstrand cross-linking drug. They found that the tumor suppressor and transcriptional regulator p53 promoted apoptosis but that Wnt promoted a competing, p53-independent survival signal. DNA damage suppressed the activity of casein kinase 1α (Csnk1a1 or CK1α), a kinase that phosphorylates β-catenin, promoting its degradation and thereby inhibiting Wnt signaling. These findings show that pro- and antiapoptotic signals from independent pathways compete to regulate cell survival in response to DNA damage.
Citation: J. Carreras Puigvert, L. von Stechow, R. Siddappa, A. Pines, M. Bahjat, L. C. J. M. Haazen, J. V. Olsen, H. Vrieling, J. H. N. Meerman, L. H. F. Mullenders, B. van de Water, E. H. J. Danen, Systems Biology Approach Identifies the Kinase Csnk1a1 as a Regulator of the DNA Damage Response in Embryonic Stem Cells. Sci. Signal.6, ra5 (2013).
Nam Hee Kim, Hyun Sil Kim, Nam-Gyun Kim, Inhan Lee, Hyung-Seok Choi, Xiao-Yan Li, Shi Eun Kang, So Young Cha, Joo Kyung Ryu, Jung Min Na, Changbum Park, Kunhong Kim, Sanghyuk Lee, Barry M. Gumbiner, Jong In Yook, and Stephen J. Weiss (1 November 2011) Sci. Signal.4 (197), ra71.
[DOI: 10.1126/scisignal.2001744] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »