SUMOylation negatively regulates transcriptional and oncogenic activities of MafA.

Abstract

Dysregulated expression of Maf proteins (namely c-Maf, MafA and MafB) leads to multiple myeloma in humans and oncogenic transformation of chicken embryonic fibroblasts. Maf proteins are transcriptional activators of tissue-specific gene expression and regulators of cell differentiation. For example, MafA is a critical regulator of crystallin genes and the lens differentiation program in chickens. In mammals, MafA is essential for the development of mature insulin-producing beta-cells of pancreas. It has been shown that MafA protein stability is regulated by phosphorylations at multiple serine and threonine residues. Here, we report that Maf proteins are also post-translationally modified by small ubiquitin-like modifier (SUMO) proteins at a conserved lysine residue in the amino-terminal transactivator domain. A SUMOylation-deficient mutant of MafA (K32R) was more potent than wild-type MafA in transactivating luciferase reporter construct driven by alphaA-crystallin or insulin gene promoter. In ovo electroporation into developing chicken embryo showed that the K32R mutant induced ectopic delta-crystallin gene expression more efficiently than the wild-type MafA. We also demonstrated that the K32R mutant had enhanced ability to induce colony formation of a chicken fibroblast cell line DF-1. Therefore, SUMOylation is a functional post-translational modification of MafA that negatively regulates its transcriptional and transforming activities.

• Authors: Kenichi Kanai, Hasan Mahmud Reza, Akiyo Kamitani, Yuri Hamazaki, Song-iee Han, Kunio Yasuda, Kohsuke Kataoka
• Journal: Genes to cells : devoted to molecular & cellular mechanisms (Genes Cells) Vol. 15 Issue 9 Pg. 971-82 (Sep 01 2010) ISSN: 1365-2443 [Electronic] England
• PMID: 20718938 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Maf Transcription Factors, Large
• MafB Transcription Factor
• Mafa protein, mouse
• Small Ubiquitin-Related Modifier Proteins
• delta-Crystallins
• Lysine

Topics

• Animals
• Cell Line
• Cell Line, Tumor
• Cell Transformation, Neoplastic (genetics)
• Chick Embryo
• Fibroblasts (cytology, metabolism)
• Gene Expression Regulation, Developmental
• HeLa Cells
• Humans
• Lysine (genetics, metabolism)
• Maf Transcription Factors, Large (genetics, metabolism)
• MafB Transcription Factor (genetics, metabolism)
• Mice
• Mutation
• NIH 3T3 Cells
• Small Ubiquitin-Related Modifier Proteins (genetics, metabolism)
• Sumoylation
• Transcription, Genetic (genetics)
• Transfection
• delta-Crystallins (genetics)