Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation.

Abstract:

:In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3-/- mice, Stat3 is constitutively acetylated and naive CD4+ T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

journal_name

Mol Cell

journal_title

Molecular cell

authors

Ma L,Huang C,Wang XJ,Xin DE,Wang LS,Zou QC,Zhang YS,Tan MD,Wang YM,Zhao TC,Chatterjee D,Altura RA,Wang C,Xu YS,Yang JH,Fan YS,Han BH,Si J,Zhang X,Cheng J,Chang Z,Chin YE

doi

10.1016/j.molcel.2016.12.002

subject

Has Abstract

pub_date

2017-01-19 00:00:00

pages

296-309

issue

2

eissn

1097-2765

issn

1097-4164

pii

S1097-2765(16)30815-2

journal_volume

65

pub_type

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