The Forkhead Transcription Factor Foxl2 Is Sumoylated in Both Human and Mouse: Sumoylation Affects Its Stability, Localization, and Activity

The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gona...

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Published in:PloS one Vol. 5; no. 3; p. e9477
Main Authors: Marongiu, Mara, Deiana, Manila, Meloni, Alessandra, Marcia, Loredana, Puddu, Alessandro, Cao, Antonio, Schlessinger, David, Crisponi, Laura
Format: Journal Article
Language:English
Published: United States Public Library of Science 02.03.2010
Public Library of Science (PLoS)
Subjects:
Animal care
Animal tissues
Animals
Antagonism
Blepharophimosis
Cell lines
Chlorocebus aethiops
Cloning
COS Cells
Deactivation
Deoxyribonucleic acid
DNA
Forkhead Box Protein L2
Forkhead protein
Forkhead Transcription Factors - metabolism
Gene expression
Gene Expression Profiling
Gene Expression Regulation
Genetics and Genomics/Animal Genetics
Genetics and Genomics/Gene Function
Granulosa cells
Humans
Inactivation
Localization
Male
Mice
Mice, Inbred C57BL
Molecular Biology/Post-Translational Regulation of Gene Expression
Mutation
Penicillin
Protein Inhibitors of Activated STAT - metabolism
Proteins
Reproductive status
Sex determination
Sox9 protein
Spermatogenesis
Stability
SUMO protein
SUMO-1 Protein
Transcription factors
Ubiquitin-Conjugating Enzyme UBC9
Ubiquitin-Conjugating Enzymes - metabolism
Yeast
Italy
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES) and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.
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Conceived and designed the experiments: MM LC. Performed the experiments: MM MD AM LM AP. Analyzed the data: MM DS LC. Contributed reagents/materials/analysis tools: AC LC. Wrote the paper: MM DS LC.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0009477