RT Journal Article
SR Electronic
T1 HDAC11 regulates type I interferon signaling through defatty-acylation of SHMT2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 211706
DO 10.1101/211706
A1 Ji Cao
A1 Lei Sun
A1 Pornpun Aramsangtienchai
A1 Nicole A. Spiegelman
A1 Xiaoyu Zhang
A1 Edward Seto
A1 Hening Lin
YR 2017
UL http://biorxiv.org/content/early/2017/10/31/211706.abstract
AB The smallest histone deacetylase (HDAC) and the only class IV HDAC member, HDAC11, is reported to regulate immune activation and tumorigenesis, yet its physiological function is largely unknown. Here we identify HDAC11 as an efficient lysine defatty-acylase that is >10,000-fold more efficient than its deacetylase activity. Through proteomics studies, we identified SHMT2 as a defatty-acylation substrate of HDAC11. HDAC11-catalyzed defatty-acylation did not affect the enzymatic activity of SHMT2. Instead, it affects the ability of SHMT2 to regulate type I interferon receptor ubiquitination and internalization. Correspondingly, HDAC11 depletion increased type I interferon signaling in both cell culture and mice. This study is the first time a zinc-dependent HDAC is found to have an activity that is much more efficient than the corresponding deacetylase activity. The finding expands the physiological functions of HDAC11 and protein lysine fatty acylation, and opens up opportunities to develop HDAC11-specific inhibitors as therapeutics to modulate immune responses.