The Arf tumor suppressor regulates platelet-derived growth factor receptor beta signaling: a new view through the eyes of Arf(-/-) mice.
Arf is a key mammalian tumor suppressor gene known to be activated in response to aberrant mitogenic signals leading to both p53-dependent and -independent effects. We recently uncovered a new and somewhat unexpected function for mouse Arf as a regulator of mural cell accumulation within an ocular vascular bed destined to regress in the postnatal period. We found that the Arf gene product, p19(Arf), blocks mural cell proliferation driven by Platelet-derived growth factor receptor beta (Pdgfrbeta) in the developing vitreous. In vivo studies and analyses of cultured cells indicate that p19(Arf) dampens the expression of Pdgfrbeta. In cultured mouse embryo fibroblasts, p19(Arf) accomplishes this independently of two established effectors - Mdm2 and p53. Our findings indicating that p19(Arf) responds to specific developmental cues to disrupt Pdgfrbeta signaling in the developing eye extend existing paradigms for Arf tumor suppressor gene biology.
Thornton
J Derek
JD
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Silva
Ricardo L A
RL
Martin
Amy C
AC
Skapek
Stephen X
SX
D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005123:Eye / Q000196:embryology / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D025803:Tumor Suppressor Protein p14ARF / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
C417743:Cdkn2a protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D020797:Receptor, Platelet-Derived Growth Factor beta