scholarly journals The Vertebrate Mitotic Checkpoint Protein BUBR1 Is an Unusual Pseudokinase

2012 ◽  
Vol 22 (6) ◽  
pp. 1321-1329 ◽  
Author(s):  
Saskia J.E. Suijkerbuijk ◽  
Teunis J.P. van Dam ◽  
G. Elif Karagöz ◽  
Eleonore von Castelmur ◽  
Nina C. Hubner ◽  
...  
Keyword(s):  
Mitotic Checkpoint ◽  
Checkpoint Protein ◽  
Mitotic Checkpoint Protein

scholarly journals Bub1 mediates cell death in response to chromosome missegregation and acts to suppress spontaneous tumorigenesis

2007 ◽  
Vol 179 (2) ◽  
pp. 255-267 ◽  
Author(s):  
Karthik Jeganathan ◽  
Liviu Malureanu ◽  
Darren J. Baker ◽  
Susan C. Abraham ◽  
Jan M. van Deursen
Keyword(s):  
Cell Death ◽  
Chromosome Segregation ◽  
Physiological Role ◽  
Mitotic Checkpoint ◽  
Critical Threshold ◽  
Wild Type ◽  
Checkpoint Protein ◽  
Chromosome Missegregation ◽  
Mitotic Checkpoint Protein

The physiological role of the mitotic checkpoint protein Bub1 is unknown. To study this role, we generated a series of mutant mice with a gradient of reduced Bub1 expression using wild-type, hypomorphic, and knockout alleles. Bub1 hypomorphic mice are viable, fertile, and overtly normal despite weakened mitotic checkpoint activity and high percentages of aneuploid cells. Bub1 haploinsufficient mice, which have a milder reduction in Bub1 protein than Bub1 hypomorphic mice, also exhibit reduced checkpoint activity and increased aneuploidy, but to a lesser extent. Although cells from Bub1 hypomorphic and haploinsufficient mice have similar rates of chromosome missegregation, cell death after an aberrant separation decreases dramatically with declining Bub1 levels. Importantly, Bub1 hypomorphic mice are highly susceptible to spontaneous tumors, whereas Bub1 haploinsufficient mice are not. These findings demonstrate that loss of Bub1 below a critical threshold drives spontaneous tumorigenesis and suggest that in addition to ensuring proper chromosome segregation, Bub1 is important for mediating cell death when chromosomes missegregate.

The human mitotic checkpoint protein BubR1 regulates chromosome–spindle attachments

2004 ◽  
Vol 7 (1) ◽  
pp. 93-98 ◽  
Author(s):  
Michael A. Lampson ◽  
Tarun M. Kapoor
Keyword(s):  
Mitotic Checkpoint ◽  
Checkpoint Protein ◽  
Mitotic Checkpoint Protein

scholarly journals Altered Expression of the Early Mitotic Checkpoint Protein, CHFR, in Breast Cancers: Implications for Tumor Suppression

2007 ◽  
Vol 67 (13) ◽  
pp. 6064-6074 ◽  
Author(s):  
Lisa M. Privette ◽  
Maria E. González ◽  
Lei Ding ◽  
Celina G. Kleer ◽  
Elizabeth M. Petty
Keyword(s):  
Tumor Suppression ◽  
Mitotic Checkpoint ◽  
Breast Cancers ◽  
Altered Expression ◽  
Checkpoint Protein ◽  
Mitotic Checkpoint Protein

scholarly journals PB2101 FUNCTIONAL SIGNIFICANCE OF OVEREXPRESSION OF MITOTIC CHECKPOINT PROTEIN BUB1 IN MULTIPLE MYELOMA

HemaSphere ◽  
2019 ◽  
Vol 3 (S1) ◽  
pp. 946-947
Author(s):  
Y. Fujibayashi ◽  
N. Sakamoto-Inada ◽  
S. Kuwahara-Ota ◽  
R. Isa ◽  
J. Yamaguchi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Functional Significance ◽  
Mitotic Checkpoint ◽  
Checkpoint Protein ◽  
Mitotic Checkpoint Protein

scholarly journals Mitotic checkpoint protein Mad1 is required for early Nup153 recruitment to chromatin and nuclear envelope integrity

2020 ◽  
Author(s):  
Ikram Mossaid ◽  
Guillaume Chatel ◽  
Valérie Martinelli ◽  
Marcela Vaz ◽  
Birthe Fahrenkrog
Keyword(s):  
Nuclear Envelope ◽  
Three Dimensional ◽  
Time Lapse ◽  
Mitotic Checkpoint ◽  
Membrane Curvature ◽  
Nuclear Pore ◽  
Structured Illumination ◽  
Electron Microscopic ◽  
Checkpoint Protein ◽  
Mitotic Checkpoint Protein

AbstractThe nucleoporin Nup153 is a multifunctional protein and the mitotic checkpoint protein Mad1one of its many binding partners. The functional relevance of their interaction has remained elusive. Here, we have further dissected Nup153’s and Mad1’s interface and functional interplay. By in situ proximity ligation assays, we found that the presence of a nuclear envelope (NE) is prerequisite for the Nup153-Mad1 interaction. Time-lapse microscopy revealed that depletion of Mad1 delayed recruitment of Nup153 to anaphase chromatin, which was often accompanied by a prolongation of anaphase. Furthermore, as seen by electron microscopic and three-dimensional structured illumination investigations, Nup153 and Mad1 depletion led to alterations in NE architecture, characterised by a change of the membrane curvature at nuclear pore complexes (NPCs) and an expansion of the spacing between the inner and outer nuclear membranes. Nup153 depletion, but not of Mad1, caused defects in interphase NPC assembly with partial displacement of cytoplasmic nucleoporins and a reduction in NPC density. Together our results suggest that Nup153 has separable roles in NE and NPC formation: in post-mitotic NE reformation in concert with Mad1 and in interphase NPC assembly, independent of Mad1.SummaryThe mitotic checkpoint protein is required for Nup153 recruitment to anaphase chromatin and in turn post-mitotic, but not interphase nuclear pore complex assembly.

scholarly journals Mitotic checkpoint protein Mad1 is required for early Nup153 recruitment to chromatin and nuclear envelope integrity

2020 ◽  
Vol 133 (21) ◽  
pp. jcs249243
Author(s):  
Ikram Mossaid ◽  
Guillaume Chatel ◽  
Valérie Martinelli ◽  
Marcela Vaz ◽  
Birthe Fahrenkrog
Keyword(s):  
Nuclear Envelope ◽  
Three Dimensional ◽  
Time Lapse ◽  
Mitotic Checkpoint ◽  
Membrane Curvature ◽  
Nuclear Pore ◽  
Structured Illumination ◽  
Electron Microscopic ◽  
Checkpoint Protein ◽  
Mitotic Checkpoint Protein

ABSTRACTNucleoporin Nup153 is a multifunctional protein and a known binding partner of mitotic checkpoint protein Mad1 (also known as MAD1L1). The functional relevance of their interaction has remained elusive. Here, we have further dissected the interface and functional interplay of Nup153 and Mad1. Using in situ proximity ligation assays, we found that the presence of a nuclear envelope (NE) is a prerequisite for the Nup153–Mad1 association. Time-lapse microscopy revealed that depletion of Mad1 delayed recruitment of Nup153 to anaphase chromatin, which was often accompanied by a prolongation of anaphase. Furthermore, as seen by electron microscopic and three-dimensional structured illumination investigations, Nup153 and Mad1 depletion led to alterations in NE architecture, characterised by a change of membrane curvature at nuclear pore complexes (NPCs) and an expansion of the spacing between inner and outer nuclear membranes. Nup153 depletion, but not Mad1 depletion, caused defects in interphase NPC assembly, with partial displacement of cytoplasmic nucleoporins and a reduction in NPC density. Taken together, our results suggest that Nup153 has separable roles in NE and NPC formation: in post-mitotic NE re-formation in concert with Mad1 and in interphase NPC assembly, independent of Mad1.

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