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Sci. Signal., 23 June 2009
Vol. 2, Issue 76, p. ra29
[DOI: 10.1126/scisignal.2000405]

RESEARCH ARTICLES

The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling

Helen Oi-Lam Cheung1,2*, Xiaoyun Zhang1, Ana Ribeiro3, Rong Mo1, Shigeru Makino1{dagger}, Vijitha Puviindran1, Kelvin K. L. Law1,2, James Briscoe3, and Chi-chung Hui1,2{ddagger}

1 Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1L7.
2 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
3 Division of Developmental Neurobiology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.

* Present address: Division of Stem Cell and Developmental Biology, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 1L7.

{dagger} Present address: RIKEN BioResource Centre, Tsukuba 305-0074, Japan.

Abstract: From insects to humans, the Hedgehog (Hh) signaling pathway has conserved roles in embryonic development and tissue homeostasis. However, it has been suggested that the lack of mammalian equivalents of Costal2 (Cos2) contributes to a divergence between the mechanism of Drosophila and mammalian Hh signal transduction. Here, we challenge this view by showing that the kinesin protein Kif7 is a critical regulator of Hh signaling in mice. Similar to Cos2, Kif7 physically interacted with Gli transcription factors and controlled their proteolysis and stability, and acted both positively and negatively in Hh signaling. Thus, Kif7 is a missing component of the mammalian Hh signaling machinery, implying a greater commonality between the Drosophila and mammalian system than the prevailing view suggests.

{ddagger} To whom correspondence should be addressed. E-mail: cchui{at}sickkids.ca

Citation: H. O.-L. Cheung, X. Zhang, A. Ribeiro, R. Mo, S. Makino, V. Puviindran, K. K. L. Law, J. Briscoe, C.-c. Hui, The Kinesin Protein Kif7 Is a Critical Regulator of Gli Transcription Factors in Mammalian Hedgehog Signaling. Sci. Signal. 2, ra29 (2009).

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