Promyelocytic leukemia protein targets MK2 to promote cytotoxicity

ABSTRACT: Promyelocytic leukemia protein (PML) is a tumor suppressor possessing multiple modes of action, including induction of apoptosis. We unexpectedly find that PML promotes necroptosis in addition to apoptosis, with Pml-/- macrophages being more resistant to TNF-mediated necroptosis than wild-type counterparts and PML-deficient mice displaying resistance to TNF-induced systemic inflammatory response syndrome. Reduced necroptosis in PML-deficient cells is associated with attenuated receptor-interacting protein kinase 1 (RIPK1) activation, as revealed by reduced RIPK1[S166] phosphorylation, and attenuated RIPK1-RIPK3-MLKL necrosome complex formation. We show that PML deficiency leads to enhanced TNF-induced MAPK activated kinase 2 (MK2) activation and elevated RIPK1[S321] phosphorylation, whi

SUBMITTER: Prof. Ming-Zong Lai 

PROVIDER: S-SCDT-EMBOR-2020-52254V1 | biostudies-other |

REPOSITORIES: biostudies-other