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Sumoylation Regulates Multiple Transcription Factors to Control Lens Differentiation
Author(s) -
LI David,
Gong Lili,
Ji Weike,
Deng Mi,
Hu Xiao-Hui,
Hu Wenfeng,
Chen Peichao,
Hu Shujun
Publication year - 2012
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.26.1_supplement.535.14
Subject(s) - sumo protein , biology , microbiology and biotechnology , cellular differentiation , transcription factor , gene isoform , transcription (linguistics) , genetics , gene , ubiquitin , linguistics , philosophy
The mammalian small ubiquitin‐like modifier SUMO contains three major isoforms that can be conjugated to a board range of substrates. However, whether SUMO1 and SUMO2 have similar or different roles in regulating differentiation remains unknown. Using vertebrate lens as a testing system, we demonstrate here for the first time that SUMO1 and SUMO2 display distinct roles in mediating lens differentiation. First, SUMO1 is more abundant than SUMO2 with distinct cellular localizations and conjugation patterns during mouse lens differentiation; Second, SUMO1 but not SUMO2 occupied the major crystallin gene promoters. Third, in an FGF‐induced cell differentiation model, increased SUMO1‐ but decreased SUMO2‐modifications were observed in multiple protein species and overexpression of SUMO‐2 but not SUMO‐1 inhibits FGF‐induced cell differentiation. Mechanistically, we demonstrate for the first time that SUMO‐1 and SUMO‐2 differentially regulates Pax‐6, an important transcription factor involved in control of brain and eye development. Furthermore, sumoylation also modulates SP‐1, Maf‐1 and Prox‐1 to control expression of the differentiation‐related genes. Together, our results establish distinct roles of SUMO1 and SUMO2 in regulating cell differentiation. Mechanistically, sumoylation modulates several transcription factors to regulate cell differentiation. (Supported by NIH Grant 1R01EY018380)