BUB1B

BUB1B（budding uninhibited by benzimidazoles 1 beta）は、ヒトではBUB1B遺伝子にコードされる酵素（プロテインキナーゼ）である。BubR1としても知られ、有糸分裂時に紡錘体チェックポイント（SAC）やキネトコア-微小管相互作用において機能し、染色体の移動と整列を促進するタンパク質として認識されている。BubR1は娘細胞への染色体の適切な分離を保証することで、有糸分裂の正確性を高め、異数性が生じないよう保護している。BubR1は腫瘍形成を防ぐことが提唱されている。 BUB1Bは紡錘体チェックポイント機能や染色体分離（英語版）に関与するプロテインキナーゼである。このタンパク質はキネトコアに局在し、後期促進複合体（APC/C）を阻害する役割を果たしており、有糸分裂後期の開始を遅らせて適切な染色体分離を保証している。紡錘体チェックポイントの機能不全は多くの種類のがんでみられる。 マウスでは、BubR1の発現上昇によって健康寿命の伸長がみられる。 BubR1は、がん、老化、多彩異数性モザイク（mosaic variegated aneuploidy、MVA）、心疾患など、さまざまな生物学的過程や病理への関与が示唆されている。BubR1タンパク質レベルは年齢とともに低下することが示されている。さらに、若年個体でのBubR1の喪失は、老化の加速や加齢関連疾患の早期発症、心機能不全、創傷治癒の遅れ、白内障、脊柱後弯、脂肪喪失や筋消耗（悪液質）、がんなどと関係する。このことはマウスで示されている。 化学放射線療法（CRT）は治癒目的で化学療法と放射線療法を併用する治療法であり、さまざまながんの治療で利用されている。CRTはがん細胞にDNA損傷を誘発することで作用する。膀胱がんの治療前の患者から採取された腫瘍試料と同じ患者のCRT後に再発した試料との比較では、CRT後再発試料ではBUB1Bの発現レベルが増加していることが示されている。こうした発現上昇は代替非相同末端結合（A-NHEJ）と呼ばれる不正確なDNA修復過程を促進すると考えられており、CRTによって引き起こされたDNA損傷が不正確に修復されることでさらなる変異が引き起こされ、腫瘍にCRT抵抗性が誘発されている可能性がある。 BUB1Bは次に挙げる因子と相互作用することが示されている。 AP2B1（英語版） BRCA2 BUB3 CDC20 MAD2L1（英語版） CBP（英語版） SIRT2（英語版） PLK1 PP2A-B56 HDAC1（英語版） HDAC2（英語版）/HDAC3（英語版） SNCG（英語版） ^ a b c GRCh38: Ensembl release 89: ENSG00000156970 - Ensembl, May 2017 ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040084 - Ensembl, May 2017 ^ Human PubMed Reference: ^ Mouse PubMed Reference: ^ “The mouse mitotic checkpoint gene bub1b, a novel bub1 family member, is expressed in a cell cycle-dependent manner”. 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Journal of Cell Science 114 (Pt 24): 4385–4395. (December 2001). doi:10.1242/jcs.114.24.4385. PMID 11792804.  Human BUB1B genome location and BUB1B gene details page in the UCSC Genome Browser.