Degradation of lung adenoma susceptibility 1, a major candidate mouse lung tumor modifier, is required for cell cycle progression.
We have previously identified murine lung adenoma susceptibility 1 (Las1) as the pulmonary adenoma susceptibility 1 candidate gene. Las1 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 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 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 Las-B6 has important implications for its intracellular function and may eventually explain Las1-A/J in lung tumorigenesis.
Liu
Yan
Y
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Vikis
Haris G
HG
Yi
Yijun
Y
Futamura
Manabu
M
Wang
Yian
Y
You
Ming
M
D000483:Alleles; D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D002522:Chlorocebus aethiops; D051379:Mice; D008938:Mitosis; D041681:NIH 3T3 Cells; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D014404:Tubulin / Q000032:analysis / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
C487460:Las1 protein, mouse; D014404:Tubulin; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex