Open AccessThe conserved ancient role of chordate PIAS as a multilevel repressor of the NF-κB pathway
Author(s) -
Ruihua Wang,
Shengfeng Huang,
Xianan Fu,
Guangrui Huang,
Xinyu Yan,
Zirui Yue,
Shangwu Chen,
Yingqiu Li,
Anlong Xu
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-16624-7
Subject(s) - chordate , biology , gene , repressor , microbiology and biotechnology , vertebrate , computational biology , genetics , gene expression
In vertebrates, PIAS genes encode versatile cellular regulators, with functions extremely complex and redundant. Here we try to understand their functions from an evolutionary perspective. we evaluate the sequences, expression and molecular functions of amphioxus PIAS genes and compare them with their vertebrate counterparts. Phylogenetic analysis suggests a single PIAS gene in ancestral chordates, which has been duplicated into four families ( PIAS1-4 ) in vertebrates by 2R-WGD but remained single in a basal chordate (amphioxus). Amphioxus PIAS encodes two variants with and without a Serine/Threonine-rich tail, which are retained in human PIAS1-3 but lost in PIAS4 . We show that amphioxus PIAS binds C-terminus of NF-κB Rel and blocks the DNA binding activity. In humans, such function is retained in PIAS1, altered in PIAS4, and lost in PIAS2-3. Instead, PIAS3 has evolved new ability to inhibit Rel by binding RHD and promoting SUMOylation. We show that amphioxus PIAS also inhibits NF-κB by binding with upstream signalling adaptor TICAM-like and MyD88. Finally, we verify that human PIAS1, 3 and 4, but not 2, were capable of these newly-discovered functions. Our study offers insight into the sub- and neo-functionalization of PIAS genes and suggests a conserved ancient role for chordate PIAS in NF-κB signalling.