title: Control of the hippo pathway by Set7-dependent methylation of Yap.
abstract: Methylation of nonhistone proteins is emerging as a regulatory mechanism to control protein function. Set7 (Setd7) is a SET-domain-containing lysine methyltransferase that methylates and alters function of a variety of proteins in vitro, but the in vivo relevance has not been established. We found that Set7 is a modifier of the Hippo pathway. Mice that lack Set7 have a larger progenitor compartment in the intestine, coinciding with increased expression of Yes-associated protein (Yap) target genes. Mechanistically, monomethylation of lysine 494 of Yap is critical for cytoplasmic retention. These results identify a methylation-dependent checkpoint in the Hippo pathway.
authors.affiliation: The Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Menno J
authors.initials: MJ
authors.lastname: Oudhoff
authors.forename: Spencer A
authors.initials: SA
authors.lastname: Freeman
authors.forename: Amber L
authors.initials: AL
authors.lastname: Couzens
authors.forename: Frann
authors.initials: F
authors.lastname: Antignano
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Kuznetsova
authors.forename: Paul H
authors.initials: PH
authors.lastname: Min
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Northrop
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lehnertz
authors.forename: Dalia
authors.initials: D
authors.lastname: Barsyte-Lovejoy
authors.forename: Masoud
authors.initials: M
authors.lastname: Vedadi
authors.forename: Cheryl H
authors.initials: CH
authors.lastname: Arrowsmith
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishina
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gold
authors.forename: Fabio M V
authors.initials: FM
authors.lastname: Rossi
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gingras
authors.forename: Colby
authors.initials: C
authors.lastname: Zaph
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D000090683:Hippo Signaling Pathway; D011495:Histone-Lysine N-Methyltransferase; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011496:Protein Methyltransferases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C562044:Setd7 protein, mouse; D017346:Protein Serine-Threonine Kinases