title: Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2.
abstract: Cellular identity in metazoan organisms is frequently established through lineage-specifying transcription factors, which control their own expression through transcriptional positive feedback, while antagonizing the developmental networks of competing lineages. Here, we have uncovered a distinct positive feedback loop that arises from the reciprocal stabilization of the tyrosine kinase ABL and the transcriptional coactivator TAZ. Moreover, we determined that this loop is required for osteoblast differentiation and embryonic skeletal formation. ABL potentiated the assembly and activation of the RUNX2-TAZ master transcription factor complex that is required for osteoblastogenesis, while antagonizing PPARγ-mediated adipogenesis. ABL also enhanced TAZ nuclear localization and the formation of the TAZ-TEAD complex that is required for osteoblast expansion. Last, we have provided genetic data showing that regulation of the ABL-TAZ amplification loop lies downstream of the adaptor protein 3BP2, which is mutated in the craniofacial dysmorphia syndrome cherubism. Our study demonstrates an interplay between ABL and TAZ that controls the mesenchymal maturation program toward the osteoblast lineage and is mechanistically distinct from the established model of lineage-specific maturation.
authors: Yoshinori
authors: Y
authors: Matsumoto
authors: Jose
authors: J
authors: La Rose
authors: Oliver A
authors: OA
authors: Kent
authors: Melany J
authors: MJ
authors: Wagner
authors: Masahiro
authors: M
authors: Narimatsu
authors: Aaron D
authors: AD
authors: Levy
authors: Mitchell H
authors: MH
authors: Omar
authors: Jiefei
authors: J
authors: Tong
authors: Jonathan R
authors: JR
authors: Krieger
authors: Emily
authors: E
authors: Riggs
authors: Yaryna
authors: Y
authors: Storozhuk
authors: Julia
authors: J
authors: Pasquale
authors: Manuela
authors: M
authors: Ventura
authors: Behzad
authors: B
authors: Yeganeh
authors: Martin
authors: M
authors: Post
authors: Michael F
authors: MF
authors: Moran
authors: Marc D
authors: MD
authors: Grynpas
authors: Jeffrey L
authors: JL
authors: Wrana
authors: Giulio
authors: G
authors: Superti-Furga
authors: Anthony J
authors: AJ
authors: Koleske
authors: Ann Marie
authors: AM
authors: Pendergast
authors: Robert
authors: R
authors: Rottapel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002636:Cherubism / Q000235:genetics / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; C493716:Runx2 protein, mouse; C484644:Sh3bp2 protein, mouse; D015534:Trans-Activators; C517794:Wwtr1 protein, mouse; D016315:Proto-Oncogene Proteins c-abl