Histone Deacetylase 8 Safeguards the Human Ever-shorter Telomeres 1B (hEST1B) Protein from Ubiquitin-mediated Degradation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2006 Jul 1

PMID 16809764

Citations 41

Authors

Heehyoung Lee

Nilanjan Sengupta

Alejandro Villagra

Natalie Rezai-Zadeh

Edward Seto

Affiliations

Soon will be listed here.

Abstract

Histone deacetylases (HDACs) are enzymes that regulate the functions of histones as well as nonhistones by catalyzing the removal of acetyl groups from lysine residues. HDACs regulate many biological processes, including the cell division cycle and tumorigenesis. Although recent studies have implicated HDAC8 in tumor cell proliferation, the molecular mechanisms linking HDAC8 to cell growth remain unknown. Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. Phosphorylated HDAC8 preferentially recruits Hsp70 to a complex that inhibits the CHIP (C-terminal heat shock protein interacting protein) E3 ligase-mediated degradation of hEST1B. Importantly, HDAC8 regulation of hEST1B protein stability modulates total telomerase enzymatic activity. Our findings reveal a novel mechanism by which HDAC8 contributes to tumorigenesis by regulating telomerase activity.

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