Heat Shock-induced Phosphorylation of TAR DNA-binding Protein 43 (TDP-43) by MAPK/ERK Kinase Regulates TDP-43 Function.

ABSTRACT: TAR DNA-binding protein (TDP-43) is a highly conserved and essential DNA- and RNA-binding protein that controls gene expression through RNA processing, in particular, regulation of splicing. Intracellular aggregation of TDP-43 is a hallmark of amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. This TDP-43 pathology is also present in other types of neurodegeneration including Alzheimer's disease. We report here that TDP-43 is a substrate of MEK, a central kinase in the MAPK/ERK signaling pathway. TDP-43 dual phosphorylation by MEK, at threonine 153 and tyrosine 155 (p-T153/Y155), was dramatically increased by the heat shock response (HSR) in human cells. HSR promotes cell survival under proteotoxic conditions by maintaining protein homeostasis and preve

SUBMITTER: Li W 

PROVIDER: S-EPMC5377819 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature