Gallagher Stuart J, Kefford Richard F, Rizos Helen
Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, NSW 2145, Australia.
Int J Biochem Cell Biol. 2006;38(10):1637-41. doi: 10.1016/j.biocel.2006.02.008. Epub 2006 Feb 28.
The ARF tumour suppressor is a product of the INK4a/ARF locus; a sequence that is frequently altered in human cancer. ARF is upregulated by oncogenic stimuli and is a critical regulator of p53 stability through interactions with the mdm2 and ARF-BP1/Mule ubiquitin ligases. Cellular stress signals liberate ARF from the nucleolus where it is bound to B23/nucleophosmin. This nucleolar location of ARF may serve as a reservoir for the rapid induction of p53, but may also serve to co-ordinate effects on cell cycle, survival and growth. The biological functions of ARF interactions with other binding partners remain uncertain, but ARF-mediated sumoylation may represent a unifying effector pathway.
ARF肿瘤抑制因子是INK4a/ARF基因座的产物；该序列在人类癌症中经常发生改变。ARF由致癌刺激上调，并且通过与mdm2和ARF-BP1/Mule泛素连接酶相互作用，是p53稳定性的关键调节因子。细胞应激信号将ARF从与B23/核磷蛋白结合的核仁中释放出来。ARF的这种核仁定位可能作为p53快速诱导的储存库，但也可能用于协调对细胞周期、存活和生长的影响。ARF与其他结合伙伴相互作用的生物学功能仍不确定，但ARF介导的SUMO化可能代表一种统一的效应途径。
