CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53
CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53
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DOI：
10.1074/jbc.m204177200
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发表时间：
2002-10-04
影响因子：
4.8
通讯作者：
Wadhwa, R
中科院分区：
文献类型：
--
作者：
Hasan, MK;Yaguchi, T;Wadhwa, R
染色体9 p21上的INK 4a基因座编码两种结构上不同的肿瘤抑制蛋白，p16（INK 4a）和替代阅读框架蛋白ARF（小鼠中的p19（ARF）和人中的p14（ARF））。这些蛋白质中的每一种都在原代细胞的衰老中起作用，并激活细胞周期控制和肿瘤抑制的途径。目前流行的模型提出p19（ARF）通过拮抗MDM 2对其的降解来激活p53功能。然而，最近的研究表明，p14 ARF对p53的稳定作用不依赖于MDM 2重新定位到核仁。我们已经确定了一个新的合作者的ARF，CARF。它在核仁中与ARF共定位并相互作用。我们证明CARF与ARF共调节，在激活p53中与ARF合作，从而作为ARF-p53-p21通路的新组分。
The INK4a locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF (p19(ARF) in mouse and p14(ARF) in human). Each of these proteins has a role in senescence of primary cells and activates pathways for cell cycle control and tumor suppression. The current prevailing model proposes that p19(ARF) activates p53 function by antagonizing its degradation by MDM2. It was, however, recently shown that stabilization of p53 by p14ARF occurs independent of the relocalization of MDM2 to the nucleolus. We have identified a novel collaborator of ARF, CARF. It co-localizes and interacts with ARF in the nucleolus. We demonstrate that CARF is co-regulated with ARF, cooperates with it in activating p53, and thus acts as a novel component of the ARF-p53-p21 pathway.