Article: JimMY on the stage: Linking DNA damage with cell adhesion and motility

Cellular DNA undergoes constant assault from a wide range of genotoxic stress. In order to maintain genome integrity, cells develop a repertoire of sophisticated systems to detect DNA damage and mediate cellular responses to DNA damage. Defects in the DNA damage response have been implicated in a variety of disorders including aging and cancer. Tumor suppressor p53 is a key intermediate in DNA damage response by inducing cell cycle arrest to allow repair or promoting apoptosis to eliminate irreparably damaged cells. A recent study described a novel layer of p53-mediated cellular response to DNA damage, i.e., modulation of cell adhesion and motility. JMY, a p53 co-factor, was demonstrated to be a multifunctional protein that coordinates cell adhesion and motility with nuclear p53 response. These results suggest that abnormal JMY activity and/or localization could contribute to tumor invasion and reveal JMY as a potential therapeutic target.

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References

1.

Mukhopadhyay U, Eves R, Jia L, Mooney P, Mak A . p53 suppresses Src-induced podosome and rosette formation and cellular invasiveness through the upregulation of caldesmon. Mol Cell Biol. 2009; 29(11):3088-98. PMC: 2682007. DOI: 10.1128/MCB.01816-08. View

2.

Jackson S, Bartek J . The DNA-damage response in human biology and disease. Nature. 2009; 461(7267):1071-8. PMC: 2906700. DOI: 10.1038/nature08467. View

3.

Coutts A, Weston L, La Thangue N . A transcription co-factor integrates cell adhesion and motility with the p53 response. Proc Natl Acad Sci U S A. 2009; 106(47):19872-7. PMC: 2785259. DOI: 10.1073/pnas.0906785106. View

4.

Muller P, Caswell P, Doyle B, Iwanicki M, Tan E, Karim S . Mutant p53 drives invasion by promoting integrin recycling. Cell. 2010; 139(7):1327-41. DOI: 10.1016/j.cell.2009.11.026. View

5.

Wang S, Wang W, Chang Y, Wu C, Chao Y, Kao S . p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nat Cell Biol. 2009; 11(6):694-704. DOI: 10.1038/ncb1875. View

6.

Shikama N, Lee C, France S, Delavaine L, Lyon J, Krstic-Demonacos M . A novel cofactor for p300 that regulates the p53 response. Mol Cell. 1999; 4(3):365-76. DOI: 10.1016/s1097-2765(00)80338-x. View

7.

Rodier F, Coppe J, Patil C, Hoeijmakers W, Munoz D, Raza S . Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol. 2009; 11(8):973-9. PMC: 2743561. DOI: 10.1038/ncb1909. View

8.

Coutts A, Boulahbel H, Graham A, La Thangue N . Mdm2 targets the p53 transcription cofactor JMY for degradation. EMBO Rep. 2006; 8(1):84-90. PMC: 1796743. DOI: 10.1038/sj.embor.7400855. View

9.

Roger L, Gadea G, Roux P . Control of cell migration: a tumour suppressor function for p53?. Biol Cell. 2006; 98(3):141-52. DOI: 10.1042/BC20050058. View

10.

dAdda di Fagagna F . Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer. 2008; 8(7):512-22. DOI: 10.1038/nrc2440. View

11.

Zuchero J, Coutts A, Quinlan M, La Thangue N, Mullins R . p53-cofactor JMY is a multifunctional actin nucleation factor. Nat Cell Biol. 2009; 11(4):451-9. PMC: 2763628. DOI: 10.1038/ncb1852. View

JimMY on the Stage: Linking DNA Damage with Cell Adhesion and Motility