Selective molecular inhibition of the HDAC6 ZnF-UBP binding domain impairs multiple myeloma cell function.

ABSTRACT: Multiple myeloma is a plasma cell malignancy with a poor prognosis despite the recent development of new therapeutic options. Histone deacetylase 6 (HDAC6) is overexpressed in multiple myeloma cells and may be involved in the acquisition of resistance to conventional anti-proteasome treatments. In addition to displaying a deacetylase catalytic activity, HDAC6 plays an essential role in the regulation of autophagy and cell death by recognizing ubiquitinated motifs from misfolded proteins through its C-terminal ZnF-UBP binding domain. These defective proteins are sent to the aggresome to facilitate their degradation by autophagy. Here, we explore the role of the ZnF-UBP binding domain of HDAC6 in the function of multiple myeloma cells. A non-functional ZnF-UBP domain containing a 2-residue m

SUBMITTER: Rincon R 

PROVIDER: S-EPMC12000391 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature