H11HspB8 and Its Herpes Simplex Virus Type 2 Homologue ICP10PK Share Functions That Regulate Cell LifeDeath Decisions and Human Disease

Abstract EN

Small heat shock proteins (sHsp) also known as HspB are a large family of widely expressed proteins that contain a 90 residues domain known as α-crystallin.

Here, we focus on the family member H11/HspB8 and its herpes simplex virus type 2 (HSV-2) homologue ICP10PK, and discuss the possible impact of this relationship on human disease.

H11/HspB8 and ICP10PK are atypical protein kinases.

They share multi-functional activity that encompasses signaling, unfolded protein response (UPR) and the regulation of life cycle potential.

In melanocytes H11/HspB8 causes growth arrest.

It is silenced in a high proportion of melanoma prostate cancer, Ewing’s sarcoma and hematologic malignancies through aberrant DNA methylation.

Its restored expression induces cell death and inhibits tumor growth in xenograft models, identifying H11/HspB8 as a tumor suppressor.

This function involves the activation of multiple and distinct death pathways, all of which initiate with H11/HspB8-mediated phosphorylation of transforming growth factor β-activated kinase 1 (TAK1).

Both ICP10PK and H11/HspB8 were implicated in inflammatory processes that involve dendritic cells activation through Toll-like receptor-dependent pathways and may contribute to the onset of autoimmunity.

The potential evolutionary relationship of H11/HspB8 to ICP10PK, its impact on human disorders and the development of therapeutic strategies are discussed.