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Title: Roles for C-ABL and P53 in bone homeostasis and DNA damage response
Keywords: p53, osterix, bone, c-Abl, DNA, damage
Issue Date: 28-Aug-2006
Citation: WANG XUEYING (2006-08-28). Roles for C-ABL and P53 in bone homeostasis and DNA damage response. ScholarBank@NUS Repository.
Abstract: We identified p53, a well known tumor suppressor, as a novel regulator of bone remodeling. p53-/- mice display a high bone mass phenotype, an overall result of enhanced bone formation and increased bone resorption. p53 negatively regulates osteoblast differentiation and osteoblast-dependent osteoclastogenesis, via repressing the transcription of osterix, an essential osteoblast differentiation factor. Inactivating p53 rescues osteoblast differentiation defects of mice lacking c-Abl, a p53 interacting protein. We provide evidence that c-Abl, a non-receptor tyrosine kinase, acts at a novel step that affects most cellular events in DNA damage response. c-Abl-/- MEFs showed defects in nuclear foci assembly of adaptor proteins such as TopBP1, Brca1, activation of Chk2 and Chk1, phosphorylation of p53 at Ser15 and induction of p53 target genes, cell cycle checkpoints and DNA repair of ssDNA breaks. These findings were confirmed by c-Abl reconstitution. Further studies indicate that c-Abl functions upstream of Atm and Atr in response to DSBs and ssDNA.
Appears in Collections:Ph.D Theses (Open)

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