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Sumoylation of Sall4B, an essential stem cell transcription factor, regulates its stability, subcellular localization and transcriptional activity
Author(s) -
Yang Feikun,
Ma Yupo,
Dai Wei
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.782.4
Subject(s) - sumo protein , transcription factor , microbiology and biotechnology , gene silencing , biology , ectopic expression , rna interference , stem cell , hek 293 cells , mutant , subcellular localization , transcription (linguistics) , embryonic stem cell , cell culture , ubiquitin , gene , rna , genetics , cytoplasm , linguistics , philosophy
Sall4 is a transcription factor that plays a key role in the maintenance and self‐renewal of embryonic stem cells. However, little is known about its regulation. Sall4B, a major isoform of Sall4, was primarily ubiquitinated when ectopically expressed in HEK293T cells, and a significant fraction was further modified by sumoylation. Constitutive SUMO‐modification of Sall4B was also detected in Tera‐1 cell line. Sall4B sumoylation was independent of ubiquitination and lysine residues 156, 316, 374, and 401 were essential for sumoylation. Chromatin fraction contained more SUMO‐deficient Sall4B than wild type Sall4B. Despite a shorter half‐life than the wild‐type counterpart, SUMO‐deficient Sall4B interacted with Oct4 more efficiently. RNAi‐mediated silencing of SALL4 expression in Tera‐1 cells caused significant down‐regulation of both Oct4 and Sox2, which was rescued by ectopic expression of wild type SALL4B but not by SUMO‐deficient mutant. Significantly, compared with the wild‐type Sall4B, SUMO‐deficient mutant exhibited compromised trans‐activation or trans‐repression activities in reporter gene assays. Combined, our studies reveal sumoylation as a novel form of post‐translational modification for regulating the stability, subcellular localization and transcriptional activity of Sall4.