Degradation of lung adenoma susceptibility 1, a major candidate mouse lung tumor modifier, is required for cell cycle progression.
Degradation of lung adenoma susceptibility 1, a major candidate mouse lung tumor modifier, is required for cell cycle progression.
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肺腺瘤敏感性 1 是一种主要的候选小鼠肺肿瘤调节因子，其降解是细胞周期进展所必需的。
DOI：
10.1158/0008-5472.can-07-2574
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发表时间：
2007
期刊：
影响因子：
11.2
通讯作者：
You,Ming
中科院分区：
文献类型：
--
作者：
Liu,Yan;Vikis,HarisG;Yi,Yijun;Futamura,Manabu;Wang,Yian;You,Ming
我们先前已确定肺腺瘤易感性1（Las 1）作为肺腺瘤易感性1的候选基因。Las 1有两个天然等位基因，Las 1-A/JandLas 1-B6。Las 1编码一个85-kDa的蛋白质，具有未知的生物学功能。在本研究中，我们报告，Las 1是一个不稳定的蛋白质和Las 1的快速破坏依赖于泛素-蛋白酶体途径。Las 1是一种新的微管结合蛋白，与微管蛋白结合的Las 1未被泛素化。我们进一步表明，Las 1-A/J是一个更稳定的蛋白比Las 1-B6。Las 1在细胞周期的G2期表达，泛素-蛋白酶体介导的Las 1破坏发生在有丝分裂中。Las 1-A/J的过表达抑制正常E10细胞增殖并诱导有缺陷的胞质分裂。Las 1-A/J和Las-B6的差异降解对其细胞内功能具有重要意义，并可能最终解释Las 1-A/J在肺肿瘤发生中的作用。[Cancer Res 2007;67（21）：10207-13]
We have previously identified murinelung adenoma susceptibility 1(Las1) as the pulmonary adenoma susceptibility 1 candidate gene. Las1 has two natural alleles,Las1-A/JandLas1-B6. Las1encodes an 85-kDa protein with uncharacterized biological function. In the present study, we report that Las1 is an unstable protein and the rapid destruction of Las1 depends on the ubiquitin-proteasome pathway. Las1 is a new microtubule-binding protein and Las1 associated with tubulin is not ubiquitinated. We further show that Las1-A/J is a more stable protein than Las1-B6. Las1 is expressed in the G2phase of the cell cycle and that ubiquitin-proteasome–mediated Las1 destruction occurs in mitosis. Overexpression of Las1-A/J inhibits normal E10 cell proliferation and induces a defective cytokinesis. The differential degradation of Las1-A/J and Las-B6 has important implications for its intracellular function and may eventually explain Las1-A/J in lung tumorigenesis. [Cancer Res 2007;67(21):10207–13]