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

Cancer Res. 2007 Nov 1;67(21):10207-13. doi: 10.1158/0008-5472.CAN-07-2574.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles
  • Animals
  • COS Cells
  • Cell Cycle*
  • Chlorocebus aethiops
  • Mice
  • Mitosis
  • NIH 3T3 Cells
  • Proteasome Endopeptidase Complex / physiology
  • Tubulin / analysis
  • Tubulin / physiology
  • Tumor Suppressor Proteins / analysis
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin / metabolism


  • Las1 protein, mouse
  • Tubulin
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex