title: The kinesin protein Kif7 is a critical regulator of Gli transcription factors in mammalian hedgehog signaling.
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.
authors: Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Helen Oi-Lam
authors: HO
authors: Cheung
authors: Xiaoyun
authors: X
authors: Zhang
authors: Ana
authors: A
authors: Ribeiro
authors: Rong
authors: R
authors: Mo
authors: Shigeru
authors: S
authors: Makino
authors: Vijitha
authors: V
authors: Puviindran
authors: Kelvin K L
authors: KK
authors: Law
authors: James
authors: J
authors: Briscoe
authors: Chi-Chung
authors: CC
authors: Hui
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D004622:Embryo, Mammalian / Q000196:embryology*; D047108:Embryonic Development / Q000502:physiology*; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D015398:Signal Transduction / Q000502:physiology*; D000071676:Zinc Finger Protein GLI1
chemical_list: D029721:Drosophila Proteins; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; C502069:KIF7 protein, human; D051741:Kruppel-Like Transcription Factors; D000071676:Zinc Finger Protein GLI1; C107452:cos protein, Drosophila; D016547:Kinesins