| Note | Protein name: BUBR1 |
| |
| |  |
| |
| | Figure 2 : Schematic representation of BUBR1 showing position of mutations, with truncating mutations depicted above the protein and missense mutations below. |
| |
| Description | 1050 amino acids, 120 kDa |
| Expression | Ubiquituously expressed. |
| Localisation | Cytoplasmic in interphase cells. Bound to BUB3 or CENPE, it can be localized to nuclear kinetochores. |
| Function | A central component of the mitotic spindle checkpoint that directly inhibits the anaphase-promoting complex/cyclosome until sister chromatids are correctly attached to the spindle, thus ensuring proper chromosome segregation during cell division. Also binds the motor protein CENPE, an interaction required for regulation of kinetochore-microtubule interactions and checkpoint signalling. |
| Homology | BUBR1 is the mammalian homolog of yeast Mad3, a significant difference being that BUBR1 possesses a kinase domain which is absent in Mad3. |
| Entity | Mosaic variegated aneuploidy (MVA) |
| Note | is a rare recessive condition characterised by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay and a broad spectrum of additional congenital abnormalities and medical conditions may also occur |
| Prognosis | There is early mortality in a significant proportion of cases due to failure to thrive and/or complications of congenital abnormalities, epilepsy, infections or malignancy. |
| Cytogenetics | The proportion of aneuploid cells varies but is usually >25% and is substantially greater than in normal individuals. |
| Oncogenesis | The risk of malignancy in MVA is high, with rhabdomyosarcoma, Wilms tumour and leukaemia reported in several cases. Two of the five cases with BUB1B mutations developed an embryonal rhabdomyosarcoma. |
| | |
| Mutations of mitotic checkpoint genes in human cancers. |
| Cahill DP, Lengauer C, Yu J, Riggins GJ, Willson JK, Markowitz SD, Kinzler KW, Vogelstein B |
| Nature. 1998 ; 392 (6673) : 300-303. |
| PMID 9521327 |
| |
| Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma. |
| Limwongse C, Schwartz S, Bocian M, Robin NH |
| American journal of medical genetics. 1999 ; 82 (1) : 20-24. |
| PMID 9916837 |
| |
| Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease. |
| Plaja A, Vendrell T, Smeets D, Sarret E, Gili T, CatalˆƯ V, Mediano C, Scheres JM |
| American journal of medical genetics. 2001 ; 98 (3) : 216-223. |
| PMID 11169558 |
| |
| The spindle checkpoint, aneuploidy, and cancer. |
| Bharadwaj R, Yu H |
| Oncogene. 2004 ; 23 (11) : 2016-2027. |
| PMID 15021889 |
| |
| Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. |
| Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, Mˆ©hes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N |
| Nature genetics. 2004 ; 36 (11) : 1159-1161. |
| PMID 15475955 |
| |
| The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. |
| Lampson MA, Kapoor TM |
| Nature cell biology. 2005 ; 7 (1) : 93-98. |
| PMID 15592459 |
| |
