Atlas of Genetics and Cytogenetics in Oncology and Haematology
BUB1B (BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast))
| Identity |
| Other names | BUBR1 |
| Bub1A | |
| MAD3L | |
| Hugo | BUB1B |
| Location | 15q15 |
| DNA/RNA |
 | |
| Figure 1 : Schematic representation of BUB1B demonstrating the relative exon sizes (introns are not drawn to scale) | |
| Description | The gene spans 60 kb and is composed of 23 exons |
| Protein |
 | |
| Figure 2 : Schematic representation of BUBR1 showing position of mutations, with truncating mutations depicted above the protein and missense mutations below. | |
| Note | Protein name: BUBR1 |
| 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. |
| Mutations |
| Note | See figure 2 above |
| Germinal | Biallelic germline mutations found in five Mosaic Variegated Aneuploidy (MVA) cases. Each family carries one missense mutation and one mutation that results in premature protein truncation or an absent transcript. |
| Somatic | Deletion of T at codon 1023 predicted to remove part of the kinase domain. |
| Implicated in |
| 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. |
| External links |
| Bibliography |
| 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 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 07-2005 | Sandra Hanks, Nazneen Rahman |
| Medical Genetics Section of Cancer Genetics, Brookes Lawley Building Institute of Cancer Research, 15 Cotswold Road, Sutton Surrey, SM2 5NG, UK |
| Citation |
| This paper should be referenced as such : |
| Hanks S, Rahman N . BUB1B (BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast)). Atlas Genet Cytogenet Oncol Haematol. July 2005 . URL : http://AtlasGeneticsOncology.org/Genes/BUB1BID854ch15q15.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Jul 2 08:22:21 2008 |
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