Role of Hec1 in spindle checkpoint signaling and kinetochore recruitment of Mad1/Mad2.
The spindle checkpoint delays sister chromatid separation until all chromosomes have undergone bipolar spindle attachment. Checkpoint failure may result in chromosome mis-segregation and may contribute to tumorigenesis. We showed that the human protein Hec1 was required for the recruitment of Mps1 kinase and Mad1/Mad2 complexes to kinetochores. Depletion of Hec1 impaired chromosome congression and caused persistent activation of the spindle checkpoint, indicating that high steady-state levels of Mad1/Mad2 complexes at kinetochores were not essential for checkpoint signaling. Simultaneous depletion of Hec1 and Mad2 caused catastrophic mitotic exit, making Hec1 an attractive target for the selective elimination of spindle checkpoint-deficient cells.
D002135:Calcium-Binding Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D002877:Chromosomes, Human / Q000502:physiology / Q000648:ultrastructure; D003598:Cytoskeletal Proteins; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011505:Protein-Tyrosine Kinases; D034741:RNA, Small Interfering; D022661:RNA, Untranslated / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000502:physiology* / Q000648:ultrastructure; D020798:Two-Hybrid System Techniques
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D008869:Microtubule-Associated Proteins; C120529:NDC80 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D012097:Repressor Proteins; C068688:centromere protein E; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human