Cooperation between p27 and p107 during endochondral ossification suggests a genetic pathway controlled by p27 and p130 Journal Article


Authors: Yeh, N.; Miller, J. P.; Gaur, T.; Capellini, T. D.; Nikolich-Zugich, J.; De La Hoz, C.; Selleri, L.; Bromage, T. G.; Van Wijnen, A. J.; Stein, G. S.; Lian, J. B.; Vidal, A.; Koff, A.
Article Title: Cooperation between p27 and p107 during endochondral ossification suggests a genetic pathway controlled by p27 and p130
Abstract: Pocket proteins and cyclin-dependent kinase (CDK) inhibitors negatively regulate cell proliferation and can promote differentiation. However, which members of these gene families, which cell type they interact in, and what they do to promote differentiation in that cell type during mouse development are largely unknown. To identify the cell types in which p107 and p27 interact, we generated compound mutant mice. These mice were null for p107 and had a deletion in p27 that prevented its binding to cyclin-CDK complexes. Although a fraction of these animals survived into adulthood and looked similar to single p27 mutant mice, a larger number of animals died at birth or within a few weeks thereafter. These animals displayed defects in chondrocyte maturation and endochondral bone formation. Proliferation of chondrocytes was increased, and ectopic ossification was observed. Uncommitted mouse embryo fibroblasts could be induced into the chondrocytic lineage ex vivo, but these cells failed to mature normally. These results demonstrate that p27 carries out overlapping functions with p107 in controlling cell cycle exit during chondrocyte maturation. The phenotypic similarities between p107-/- p27D51/D51 and p107-/- p130-/- mice and the cells derived from them suggest that p27 and p130 act in an analogous pathway during chondrocyte maturation. Copyright © 2007, American Society for Microbiology, All Rights Reserved.
Keywords: controlled study; survival analysis; gene deletion; nonhuman; genetic analysis; protein function; cell proliferation; animal cell; mouse; phenotype; animals; cell cycle proteins; mice; mus; cell cycle; complex formation; cell maturation; embryo; protein protein interaction; body weight; cell differentiation; cell type; animalia; protein p27; cyclin-dependent kinase inhibitor p27; fibroblast; fibroblasts; ossification; bone and bones; osteogenesis; animals, newborn; cycline; cyclin dependent kinase inhibitor; cell cycle regulation; organ size; protein p107; protein p130; retinoblastoma-like protein p107; retinoblastoma-like protein p130; s phase; multigene family; cartilage cell; enchondral ossification; chondrocytes; chondrogenesis
Journal Title: Molecular and Cellular Biology
Volume: 27
Issue: 14
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 2007-07-01
Start Page: 5161
End Page: 5171
Language: English
DOI: 10.1128/mcb.02431-06
PUBMED: 17502351
PROVIDER: scopus
PMCID: PMC1951950
DOI/URL:
Notes: --- - "Cited By (since 1996): 6" - "Export Date: 17 November 2011" - "CODEN: MCEBD" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Andrew C Koff
    98 Koff
  2. Anxo Vidal
    7 Vidal
  3. Jeffrey P Miller
    6 Miller
  4. Nancy Yeh
    13 Yeh