Multi-lobulation of the nucleus in prolonged S phase by nuclear expression of Chk tyrosine kinase.
Chk tyrosine kinase phosphorylates Src-family tyrosine kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. To investigate the role of nuclear Chk in proliferation, various Chk mutants were constructed and expressed. Nuclear localization of Chk-induced dynamic multi-lobulation of the nucleus and prolonged S phase of the cell cycle. The N-terminal domain of Chk and a portion of its kinase domain but not the kinase activity were responsible for induction of the multi-lobulation. Cell sorting analysis revealed that nuclear multi-lobulated cells were enriched in late S phase. Multi-lobulated nuclei were surrounded with lamin B1 that was particularly concentrated in concave regions of the nuclei. Furthermore, treatment with nocodazole or taxol disrupted multi-lobulation of the nucleus. These results suggest that nuclear multi-lobulation in late S phase, which is dependent on polymerization and depolymerization of microtubules, may be involved in nuclear Chk-induced inhibition of proliferation.
Nakayama
Yuji
Y
Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8675, Japan.
Yamaguchi
Naoto
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D049109:Cell Proliferation; D048430:Cell Shape / Q000502:physiology; D018385:Centrosome / Q000378:metabolism; D002522:Chlorocebus aethiops; D019926:Cyclin B / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D034921:Lamin Type B / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000502:physiology*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D019926:Cyclin B; D034921:Lamin Type B; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases; C085377:MATK protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); D017239:Paclitaxel; D015739:Nocodazole