PML2 Overexpression Promotes Cellular Senescence in Zmpste24^−/− MEFs

The paper explored the role of the promyelocytic leukemia nuclear bodies (PML NBs) in the senes-cence of Zmpste24^−/− mouse embryonic fibroblasts (MEFs). Zmpste24^+/+ and Zmpste24^−/− MEFs overexpressing GFP, GFP-PML1 and GFP-PML2 were performed with replicative lifespan analysis, senescence-associated (SA)-β-gal staining, and the immunofluorescence detection of PML NBs morphology, proliferation marker Ki-67 and γH2AX-labeled DNA dam-age foci. The results showed that PML2 overexpression notably inhibited cell proliferation and promoted cellular senes-cence in Zmpste24^+/+ and Zmpste24^−/− MEFs, while PML1 had negligible impacts. The percentage of Ki-67-positive cells decreased, and DNA damage repair ability was compromised in PML2-expressing MEFs, and PML2 overexpression ex-erted more profound effects in inducing senescence of Zmpste24^−/− MEFs than that of Zmpste24^+/+ MEFs. Moreover, PML2 overexpression induces the formation of thread-like PML NBs in a much higher percentage of Zmpste24^−/− MEFs rather than in Zmpste24^+/+ MEFs, and these abnormal PML NBs are closely associated with cell senescence.