Groucho suppresses Pax2 transactivation by inhibition of JNK-mediated phosphorylation

被引:72
作者
Cai, Y
Brophy, PD
Levitan, I
Stifani, S
Dressler, GR [1 ]
机构
[1] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA
[3] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada
关键词
c-Jun; Groucho; N-terminal kinase; Pax2; transcription repression;
D O I
10.1093/emboj/cdg536
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Pax proteins are DNA-binding transcription factors that regulate embryonic development through the activation and repression of downstream target genes. The Pax2 gene is absolutely required for kidney development and for patterning specific regions of the nervous system such as the eye, ear and hindbrain. The Pax2/5/8 family of proteins contains both transcription activation and repression domains. The activation domain of Pax2 is phosphorylated by the c-Jun N-terminal kinase (JNK) to enhance Pax2-dependent transcription. In this report, we demonstrate that the Groucho/TLE family protein, Grg4, interacts with Pax2 to suppress transactivation. Grg4 is able to specifically inhibit phosphorylation of the Pax2 activation domain, even in the presence of activated JNK. Furthermore, the Grg4 interaction and suppression of phosphorylation depends on Pax2 binding to its target DNA sequence and is independent of histone deacetylation. These data suggest a new model for Groucho mediated suppression of transcription through the specific inhibition of modifications in the activation domain of a transactivator.
引用
收藏
页码:5522 / 5529
页数:8
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