Abstract:
:G2/M checkpoints ensure the proper timing of cell mitosis. We previously reported that p38 mitogen-activated protein kinase (MAPK) activation is essential for stress-induced G2 arrest in the U-2OS osteosarcoma cell line, but the molecular mechanism was obscure. Here, using the T7 phage display system, we find p38 directly binds to human polycomb protein 2 (HPC2), and arsenate-induced G2 arrest in U-2OS cell is p38- and phosphorylation of HPC2-dependent. Phosphorylation of HPC2 at threonine 495 is required for recruiting Ring1 and Rb family proteins to form the polycomb repressive complex (PRC), and PRC is required for arsenate-induced downregulation of CDC2 expression. Thus, p38 MAPK regulates cell cycle progression through phosphorylation of HPC2 to mediate transcriptional repression, providing a mechanistic link for arsenate-induced transcriptional silencing.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Wu W,Zhou H,He F,Xiao Z,Jiang Y,Zhao Mdoi
10.1002/1873-3468.13272subject
Has Abstractpub_date
2018-12-01 00:00:00pages
4087-4097issue
24eissn
0014-5793issn
1873-3468journal_volume
592pub_type
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