Journal article
Minibrain and Wings apart control organ growth and tissue patterning through down-regulation of Capicua
L Yang, S Paul, KG Trieu, LG Dent, F Froldi, M Forés, K Webster, KR Siegfried, S Kondo, K Harvey, L Cheng, G Jiménez, SY Shvartsman, A Veraksa
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2016
Abstract
The transcriptional repressor Capicua (Cic) controls tissue patterning and restricts organ growth, and has been recently implicated in several cancers. Cic has emerged as a primary sensor of signaling downstream of the receptor tyrosine kinase (RTK)/extracellular signal-regulated kinase (ERK) pathway, but how Cic activity is regulated in different cellular contexts remains poorly understood. We found that the kinase Minibrain (Mnb, ortholog of mammalian DYRK1A), acting through the adaptor protein Wings apart (Wap), physically interacts with and phosphorylates the Cic protein. Mnb and Wap inhibit Cic function by limiting its transcriptional repressor activity. Down-regulation of Cic by Mnb/Wa..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Iswar Hariharan for the Cic antibody; the Bloomington Drosophila Stock Center, Vienna Drosophila Resource Centre, and Developmental Studies Hybridoma Bank for their services; Walter Flores for help with preparation of Cic mutant constructs; and Jonathan Celli for help with brain size quantification. Mass spectrometry was performed at the Taplin Mass Spectrometry Facility at Harvard Medical School. This work was supported by the NIH Grants GM105813 (to A.V. and Ken Moberg) and HD085870 (to A.V. and S.Y.S.), L.Y. was supported by the University of Massachusetts Boston Sanofi Genzyme Doctoral Fellowship, S.Y.S. was supported by the NIH Grant GM086537, and G.J. is supported by Spanish Government Grant BFU2014-52863-P and Fundacio La Marato de TV3 Grant 20131730.