Functional link between retinoblastoma family of proteins and the Wnt signaling pathway in mouse epidermis.
The retinoblastoma family of proteins (pRb, p107, and p130) modulates cell cycle progression and differentiation of several tissues. We have demonstrated recently that p107 and p130 regulate keratinocyte terminal differentiation and hair follicle morphogenesis and development in vivo. This last aspect appears to be mediated by defective signaling from the mesenchyme and is associated with altered bone morphogenetic protein-4 (BMP4) -dependent signaling. However, many alterations were also found in the epithelial compartment. Given the importance of betacatenin in hair biology and in BMP signaling, we studied its expression in p107/p130-deficient skin. Although normal expression of betacatenin was found in p107/p130-deficient hair follicles, we found increased nuclear accumulation of betacatenin in the basal keratinocytes of the p107/p130-deficient mice skin. Biochemical analysis revealed that such an increase in betacatenin was due to the disruption of Axin/GSK3beta/betacatenin complexes promoted by the increased expression of Frat, the mouse homologue of GSK3betabinding protein (GBP), in epidermis, precluding the degradation of betacatenin. Collectively, these data represent the first evidence that retinoblastoma family and Wnt signaling pathways might be interconnected by functional links in skin.
Ruiz
Sergio
S
Program on Cell and Molecular Biology and Gene Therapy, CIEMAT, Madrid, Spain.
Segrelles
Carmen
C
Santos
Mirentxu
M
Lara
M Fernanda
MF
Paramio
Jesús M
JM
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004817:Epidermis / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism* / Q000637:transplantation; D018859:Hair Follicle / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D014184:Transplantation, Homologous; D051153:Wnt Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C495267:CTNNB1 protein, mouse; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491818:Frat1 protein, mouse; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; D008156:Luciferases