ERK-dependent phosphorylation of the linker and substrate-binding domain of HSP70 increases folding activity and cell proliferation.

ABSTRACT: The enhanced productive folding of translated polypeptides by heat shock protein 70 (HSP70) is often required for the survival of cancer cells. Although the folding activity of HSP70 is considered a significant determinant of the progression of cancer cells, it is still unknown how this activity could be regulated. Here, we report that the phosphorylation of HSP70 facilitates its folding activity, enhancing cell proliferation. Mass spectrometry identified the serine residues at positions 385 and 400 in the linker and substrate-binding domains of HSP70, respectively, as sites of phosphorylation mediated by EGF signaling, and this result was further confirmed by site-directed mutagenesis. ERK is known to be a specific kinase. The phosphorylation of the two sites induces the extended conforma

SUBMITTER: Lim S 

PROVIDER: S-EPMC6802635 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature