Bub1b

Symbol: Bub1b
Name: budding uninhibited by benzimidazoles 1 homolog, beta (S. cerevisiae)
Entrez gene ID: 12236
Ensembl gene ID: ENSMUSG00000040084
Species: Mouse (Taxid: 10090)

Functional description:
Essential component of the mitotic checkpoint. Required for normal mitosis progression and tumor suppression. The mitotic checkpoint delays anaphase until all chromosomes are properly attached to the mitotic spindle. One of its checkpoint functions is to inhibit the activity of the anaphase-promoting complex/cyclosome (APC/C) by blocking the binding of CDC20 to APC/C, independently of its kinase activity. The other is to monitor kinetochore activities that depend on the kinetochore motor CENPE. Required for kinetochore localization of CENPE. Negatively regulates PLK1 activity in interphase cells and suppresses centrosome amplification. Also implicated in triggering apoptosis in polyploid cells that exit aberrantly from mitotic arrest. Essential for tumor suppression. May play a role in regulating aging and fertility (By similarity). [UniProt]

Observation:

Bub1b hypomorphic mutation decreases median lifespan by 60% (from 15 to 6 months) and such mutant mice that procude low levels of the protein are prone to aneuplody and develop many phenotypes suggestive of accelerated aging, including short lifespan, growth retardation, sarcopenia, lordokyphosis, progressive bilateral cataracts, substantial loss of sub dermal adipose tissue, spinal kyphosis, muscle atrophy, reduced dermal thickness and decreased wound healing [15208629; 17272762; 16781018; 18516091].

Moreover, there is a pronounced increase in senescent associated Beta-galactosidase expression in late generation Bub1b mutant mice, indicative of increased rate of cellular senescence. Homozyogous knockout of Bub1b results in lethality, while heterozygous animals exhibit no aging phenotypes [15208629].

Sustained high-level expression of BubR1 preserves genomic integrity and reduces tumorgenesis (even in the presence of genetic alterations that strongly promote aneuplodization and cancer, such as oncogenic Ras) and extends the lifespan and delays age-related deterioriation and aneuploidy in several tissues [23242215].

BubR1 overabundance exerts its protective effect by correcting mitotic checkpoints defects [23242215].

BubR1 expression level declines with age in various tissues [15208629; 17272762; 16781018].

The median and maximum lifespan of mice with a nonsense mutation 2211insGTTA in BubR1 is significantly reduced. BubR1(+/GTTA) mice develop several aging-related phenotypes at an accelerated rate, including catarct formation, lordokyphosis, skeletal muscle wasting, impaired exercise ability, and fat loss. Further BubR1(+/GTTA) mice develop mild anaplodies and exhibit enhanced growth of carcinogen-induced tumors [Wijshake et al. 2012].



Interventions:
  • Bub1b mutation -60%
  • Bub1b overexpression +20 to +41.3%

  • Assays: Organismal Lifespan
    Median: -60
    Maximum: +20 to +41.3

    Classification:
  • Aging Differential
  • Aging-Suppressed
  • Aging-Suppressor
  • Negative Aging-Suppressor
  • Positive Aging-Suppressor


  • References:
  • 15208629: BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice.
  • 23242215: Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan.
  • 17272762: Aging-associated vascular phenotype in mutant mice with low levels of BubR1.
  • 16781018: Mutant mice with small amounts of BubR1 display accelerated age-related gliosis.
  • 18516091: Opposing roles for p16Ink4a and p19Arf in senescence and ageing caused by BubR1 insufficiency.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • BUB1B (9606)
  • BUB1B (9598)
  • BUB1B (9615)
  • BUB1B (9913)
  • Bub1b (10090)
  • Bub1b (10116)
  • BUB1B (9031)
  • sb:cb730 (7955)
  • AT2G33560 (3702)
  • Os02g0193600 (4530)

  • Inparanoids
  • ENSRNOP00000010406 (10116)
  • ENSMUSP00000037126 (10090)
  • ENSMUSP00000037126 (10090)

  • Note: The maximum lifespan of T23 mice is also significantly extended when compared with both wild-type and T-GFP controls (p = 0.05 and 0.0056).

    Edit \ Update (Admin) | Delete

    Comment on This Data Unit