RT Journal Article
SR Electronic
T1 Methods for addressing the protein-protein interaction between histone deacetylase 6 and ubiquitin
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 203372
DO 10.1101/203372
A1 Carolina dos S. Passos
A1 Nathalie Deschamps
A1 Yun Choi
A1 Robert E. Cohen
A1 Remo Perozzo
A1 Alessandra Nurisso
A1 Claudia A. Simões-Pires
YR 2017
UL http://biorxiv.org/content/early/2017/11/01/203372.abstract
AB Histone deacetylase 6 (HDAC6) is a cytoplasmic HDAC isoform able to remove acetyl groups from cellular substrates such as α-tubulin. In addition to the two deacetylase domains, HDAC6 has a C-terminal zinc-finger ubiquitin (Ub)-binding domain (ZnF-UBP) able to recognize free Ub. HDAC6-Ub interaction is thought to function in regulating the elimination of misfolded proteins during stress response through the aggresome pathway. Small molecules inhibiting deacetylation by HDAC6 were shown to reduce aggresomes, but the interplay between HDAC6 catalytic activity and Ub-binding function is not fully understood. Here we describe two methods to measure the HDAC6-Ub interaction in vitro using full-length HDAC6. Both methods were effective for screening inhibitors of the HDAC6-Ub protein-protein interaction independently of the catalytic activity. Our results suggest a potential role for the HDAC6 deacetylase domains in modulating HDAC6-Ub interaction. This new aspect of HDAC6 regulation can be targeted to address the roles of HDAC6-Ub interaction in normal and disease conditions.