Degradation of lung adenoma susceptibility 1, a major candidate mouse lung tumor modifier, is required for cell cycle progression

作者：Liu Yan; Vikis Haris G; Yi Yijun; Futamura Manabu; Wang Yian; You Ming^*

来源：Cancer Research, 2007, 67(21): 10207-10213.

DOI：10.1158/0008-5472.CAN-07-2574

dWe have previously identified murine lung adenoma susceptibility I (Las1) as the pulmonary adenoma susceptibility 1 candidate gene. Last has two natural alleles, Las1-A/J and Las1-B6. Las1 encodes an 85-kDa protein with uncharacterized biological function. In the present study, we report that Last is an unstable protein and the rapid destruction of Last depends on the ubiquitin-proteasome pathway. Last is a new microtubule-binding protein and Last associated with tubulin is not ubiquitinated. We further show that Las1-A/J is a more stable protein than Las1-B6. Last is expressed in the G(2) phase 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 LasB6 has important implications for its intracellular function and may eventually explain Las1-A/J in lung tumorigenesis.

• 出版日期2007-11-1