Essential role of RSK2 in c-Fos-dependent osteosarcoma development.
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Essential role of RSK2 in c-Fos-dependent osteosarcoma development. / David, Jean-Pierre; Mehic, Denis; Bakiri, Latifa; Schilling, Arndt; Mandic, Vice; Priemel, Matthias; Idarraga, Maria Helena; Reschke, Markus O; Hoffmann, Oskar; Amling, Michael; Wagner, Erwin F.
In: J CLIN INVEST, Vol. 115, No. 3, 3, 2005, p. 664-672.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Essential role of RSK2 in c-Fos-dependent osteosarcoma development.
AU - David, Jean-Pierre
AU - Mehic, Denis
AU - Bakiri, Latifa
AU - Schilling, Arndt
AU - Mandic, Vice
AU - Priemel, Matthias
AU - Idarraga, Maria Helena
AU - Reschke, Markus O
AU - Hoffmann, Oskar
AU - Amling, Michael
AU - Wagner, Erwin F
PY - 2005
Y1 - 2005
N2 - Inactivation of the growth factor-regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a progressive skeletal disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is associated with decreased expression of Phex, an endopeptidase regulating bone mineralization. This defect is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362 in the C-terminus. However, in the absence of RSK2, c-Fos-dependent osteosarcoma formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos protein levels, which are thought to be responsible for decreased proliferation and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas.
AB - Inactivation of the growth factor-regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a progressive skeletal disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is associated with decreased expression of Phex, an endopeptidase regulating bone mineralization. This defect is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362 in the C-terminus. However, in the absence of RSK2, c-Fos-dependent osteosarcoma formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos protein levels, which are thought to be responsible for decreased proliferation and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas.
M3 - SCORING: Zeitschriftenaufsatz
VL - 115
SP - 664
EP - 672
JO - J CLIN INVEST
JF - J CLIN INVEST
SN - 0021-9738
IS - 3
M1 - 3
ER -