| First Author | Movahedi Naini S | Year | 2015 |
| Journal | Mol Cell Biol | Volume | 35 |
| Issue | 21 | Pages | 3768-84 |
| PubMed ID | 26303530 | Mgi Jnum | J:228213 |
| Mgi Id | MGI:5705675 | Doi | 10.1128/MCB.00184-15 |
| Citation | Movahedi Naini S, et al. (2015) Group IVA Cytosolic Phospholipase A2 Regulates the G2-to-M Transition by Modulating the Activity of Tumor Suppressor SIRT2. Mol Cell Biol 35(21):3768-84 |
| abstractText | The G2-to-M transition (or prophase) checkpoint of the cell cycle is a critical regulator of mitotic entry. SIRT2, a tumor suppressor gene, contributes to the control of this checkpoint by blocking mitotic entry under cellular stress. However, the mechanism underlying both SIRT2 activation and regulation of the G2-to-M transition remains largely unknown. Here, we report the formation of a multiprotein complex at the G2-to-M transition in vitro and in vivo. Group IVA cytosolic phospholipase A2 (cPLA2alpha) acts as a bridge in this complex to promote binding of SIRT2 to cyclin A-Cdk2. Cyclin A-Cdk2 then phosphorylates SIRT2 at Ser331. This phosphorylation reduces SIRT2 catalytic activity and its binding affinity to centrosomes and mitotic spindles, promoting G2-to-M transition. We show that the inhibitory effect of cPLA2alpha on SIRT2 activity impacts various cellular processes, including cellular levels of histone H4 acetylated at K16 (Ac-H4K16) and Ac-alpha-tubulin. This regulatory effect of cPLA2alpha on SIRT2 defines a novel function of cPLA2alpha independent of its phospholipase activity and may have implications for the impact of SIRT2-related effects on tumorigenesis and age-related diseases. |
