BUB1

Overview

BUBR1 is a human gene whose product bUB1 (Budding Uninhibited by Benzimidazoles 1) is a serine/threonine-protein kinase that plays a critical role in the mitotic checkpoint (spindle assembly checkpoint), ensuring proper chromosome segregation during cell division^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}. Variants in BUBR1 have been implicated in Cancer, Congenital Disorders, Neurodegeneration. This page covers the gene’s normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.

Function

BUB1 (Budding Uninhibited by Benzimidazoles 1) is a serine/threonine-protein kinase that plays a critical role in the mitotic checkpoint (spindle assembly checkpoint), ensuring proper chromosome segregation during cell division^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}.

Key Molecular Functions

• Checkpoint signaling: BUB1 phosphorylates MAD3/BUBR1 to generate the mitotic checkpoint complex (MCC)^{2BUB1 phosphorylates MAD31999 · EMBO J · PMID 10485718Open reference}

• Kinetochore localization: BUB1 localizes to kinetochores and recruits other checkpoint proteins^{3BUB1 kinetochore localization2001 · J Cell Biol · PMID 11242036Open reference}

• Chromosome alignment: Ensures proper kinetochore-microtubule attachments^{4BUB1 and chromosome alignment2009 · Nat Cell Biol · PMID 19619488Open reference}

• Centromere function: Regulates Aurora B kinase localization and activity^{5BUB1 and Aurora B2007 · Nat Rev Cancer · PMID 17671439Open reference}

BUB1 contains:

• N-terminal kinetochore-targeting domain

• C-terminal kinase domain

• Multiple phosphorylation sites^{6BUB1 structure2008 · Nat Struct Mol Biol · PMID 18786356Open reference}

Disease Associations

Cancer

• Colorectal cancer: BUB1 mutations in microsatellite instability-high tumors^{7BUB1 in colorectal cancer2002 · Cancer Res · PMID 12124340Open reference}

• Breast cancer: Altered expression in aggressive subtypes^{8BUB1 in breast cancer2006 · Oncogene · PMID 16651469Open reference}

• Hematologic malignancies: Mutations in B-cell lymphomas and leukemias^{9BUB1 mutations in lymphoma2009 · Blood · PMID 19779462Open reference}

Congenital Disorders

• Mosaic Variegated Aneuploidy (MVA): Biallelic BUB1 mutations cause MVA syndrome^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}0

• Microcephaly: Associated with BUB1 haploinsufficiency^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}1

Neurodegeneration

• Alzheimer’s disease: Mitotic checkpoint defects in AD neurons; aneuploidy increases^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}2

• Tauopathies: BUB1 dysregulation in neurodegenerative diseases^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}3

• Aging: Declining checkpoint function contributes to genomic instability^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}4

Expression

BUB1 is expressed in proliferating cells:

• Highest: Bone marrow, testis, embryonic tissues^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}5

• Cell cycle-regulated: Peak in G2/M phase

• Low/undetectable: Most differentiated tissues

Brain expression:

• Neural progenitor cells

• Developing neurons

• Low in mature neurons

Therapeutic Implications

• Cancer therapy: BUB1 as target for anti-mitotic drugs^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}6

• Checkpoint inhibition: Synthetic lethality with microtubule poisons^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}7

• Biomarker: Checkpoint status predicts chemotherapy response^{1BUB1 and the spindle checkpoint2007 · Cell · PMID 17563350Open reference}8

See Also

• BUBR1 - Partner checkpoint kinase

• MAD2 - Checkpoint complex component

• Aurora B - Kinase partner

• Mitotic Checkpoint - Pathway

External Links

• NCBI Gene: BUB1

• UniProt: O43683

• OMIM: 602452