Faculty Collaboration Database

Degradation of lung adenoma susceptibility 1, a major candidate mouse lung tumor modifier, is required for cell cycle progression. Cancer Res 2007 Nov 01;67(21):10207-13 PMID: 17974961

Pubmed ID

17974961

Abstract

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.

Author List

Liu Y, Vikis HG, Yi Y, Futamura M, Wang Y, You M

Author

Ming You MD, PhD Associate Provost, Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

Scopus

2-s2.0-35948986310   3 Citations

MESH terms used to index this publication - Major topics in bold

Alleles
Animals
COS Cells
Cell Cycle
Cercopithecus aethiops
Mice
Mitosis
NIH 3T3 Cells
Proteasome Endopeptidase Complex
Tubulin
Tumor Suppressor Proteins
Ubiquitin