LAP2alpha-binding protein LINT-25 is a novel chromatin-associated protein involved in cell cycle exit.
Lamina-associated polypeptide 2alpha (LAP2alpha) is a nuclear protein dynamically associating with chromatin during the cell cycle. In addition, LAP2alpha interacts with A-type lamins and retinoblastoma protein and regulates cell cycle progression via the E2F-Rb pathway. Using yeast two-hybrid analysis and three independent in vitro binding assays we identified a new LAP2alpha interaction partner of hitherto unknown functions, which we termed LINT-25. LINT-25 protein levels were upregulated during G1 phase in proliferating cells and upon cell cycle exit in quiescence, senescence and differentiation. Upon cell cycle exit LINT-25 accumulated in heterochromatin foci, and LAP2alpha protein levels were downregulated by proteasomal degradation. Although LAP2alpha was not required for the upregulation and reorganization of LINT-25 during cell cycle exit, transient expression of LINT-25 in proliferating cells caused loss of LAP2alpha and subsequent cell death. Our data show a role of LINT-25 and LAP2alpha during cell cycle exit, in which LINT-25 acts upstream of LAP2alpha.
Naetar
Nana
N
Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohr-Gasse 9, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Hutter
Sabine
S
Dorner
Daniela
D
Dechat
Thomas
T
Korbei
Barbara
B
Gotzmann
Josef
J
Beug
Hartmut
H
Foisner
Roland
R
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D034882:Lamins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D020798:Two-Hybrid System Techniques
D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D034882:Lamins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C517146:OIP5 protein, human; C093413:lamina-associated polypeptide 2