DNA 二氧合酶逆转烷基化损伤
中文名称
通路描述
细胞内的 DNA 易受烷基化剂引起的各种细胞毒性和诱变性损伤。这些基因毒性化学物质会产生主要损伤，如 1-甲基腺嘌呤、3-甲基腺嘌呤、3-甲基胞嘧啶和 O6-甲基鸟嘌呤。细胞具有针对此类有毒分子的内置修复机制。例如，3-甲基腺嘌呤-DNA 糖基酶切除一些甲基化碱基，而 MGMT/hAGT 蛋白将其他损伤上的烷基基团转移到半胱氨酸残基上。大肠杆菌 AlkB 蛋白具有独特功能，其中 1-甲基腺嘌呤和 3-甲基胞嘧啶通过氧化脱羧和羟基化作用的组合进行去甲基化。AlkB 及其人类同源物 ALKBH2 (ABH2) 和 ALKBH3 (ABH3) 属于α-酮戊二酸脱氧酶家族，在α-酮戊二酸、氧气和亚铁离子的存在下氧化化学惰性化合物。作为这些化学反应的副产物，甲基化损伤会释放甲醛，而 1-乙基腺嘌呤会释放乙醛。CO2 和琥珀酸也在中间步骤中释放，但图中未显示。与其他涉及核酸酶活性的机制不同，这种修复机制通过仅去除结合在碱基上的反应性烷基基团来保留修复后的碱基，从而准确恢复受损的 DNA 序列（Trewick et al. 2002, Duncan et al. 2002, Sedgwick 2004）。
英文描述
ATF6B (ATF6-beta) activates chaperones Like its homolog ATF6 (reviewed in Fox and Andrew 2015), ATF6B is activated by cleavage in response to endoplasmic reticulum (ER) stress (Haze et al. 2001). In unstressed cells, ATF6B spans the ER membrane where its lumenal domain probably forms a complex with HSPA5 (BiP, GRP78). During ER stress, HSPA5 dissociates from ATF6B, exposing Golgi localization signals in the lumenal domain of ATF6B and causing ATF6B to traffic to the Golgi membrane. The Golgi-resident proteases MBTPS1 (S1P) and MBTPS2 (S2P) cleave ATF6B and release the cytoplasmic (N-terminal) domain, which contains a transcription activation domain, a bZIP dimerization domain, and a nuclear localization signal (Haze et al. 2001). N-glycosylation in the lumenal domain of ATF6B is required for cleavage (Guan et al. 2009). The cytoplasmic fragment transits to the nucleus where it acts as a weak transcription activator (Haze et al. 2001). By forming heterodimers with the strong activator ATF6, ATF6B may act as an inhibitory modulator of ATF6 (Thuerauf et al. 2004, Thuerauf et al. 2007). Deletion of the ER (C-terminal) domain of ATF6B in HEK293 cells causes increased production of membrane proteins, possibly due to constitutive transit of the N-terminal domain of ATF6B to the nucleus and activation of genes (Choi et al. 2025).
所含基因
4 个基因