Thornton J Derek, Silva Ricardo L A, Martin Amy C, Skapek Stephen X
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Cell Cycle. 2005 Oct;4(10):1316-9. doi: 10.4161/cc.4.10.2109. Epub 2005 Oct 17.
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.
Arf是一种关键的哺乳动物肿瘤抑制基因，已知其在响应异常有丝分裂信号时被激活，从而导致p53依赖性和非依赖性效应。我们最近发现了小鼠Arf的一种新的、有些意想不到的功能，即它作为一种调节因子，参与出生后注定会退化的眼部血管床内周细胞的积累。我们发现，Arf基因产物p19(Arf)在发育中的玻璃体中可阻断由血小板衍生生长因子受体β（Pdgfrbeta）驱动的周细胞增殖。体内研究和对培养细胞的分析表明，p19(Arf)会抑制Pdgfrbeta的表达。在培养的小鼠胚胎成纤维细胞中，p19(Arf)独立于两种已确定的效应因子——Mdm2和p53来实现这一点。我们的研究结果表明，p19(Arf)响应特定的发育信号，以破坏发育中的眼睛中的Pdgfrbeta信号传导，这扩展了Arf肿瘤抑制基因生物学的现有范例。
