The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis.
The human homologue of the yeast polyubiquitination factor Ufd2p is cleaved by caspase 6 and granzyme B during apoptosis.
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酵母多聚泛素化因子 Ufd2p 的人类同源物在细胞凋亡过程中被 caspase 6 和颗粒酶 B 切割。
DOI：
10.1042/0264-6021:3610587
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Rosen,Antony
中科院分区：
文献类型：
--
作者：
Mahoney,JamesA;Odin,JosephA;White,SarahM;Shaffer,David;Koff,Andrew;Casciola-Rosen,Livia;Rosen,Antony
在本研究中，我们证明了UFD 2 p（一种催化长聚泛素链形成的酵母蛋白，并参与对环境应激的反应），UFD 2（泛素融合降解蛋白-2）的人类同源物，在多种刺激诱导的细胞凋亡过程中被切割，包括UVB照射，Fas连接，星形孢菌素治疗和细胞毒性淋巴细胞颗粒诱导的死亡。半胱天冬酶6和颗粒酶B在Asp 123处有效地切割UFD 2 [kcat/Km=（4-5）× 104 M −1·s−1]，而半胱天冬酶3和7在Asp 123处切割UFD 2约100 μ mol/L。10-在Asp 109上游的效率降低了1倍。因此，UFD 2被添加到越来越多的具有紧密间隔的半胱天冬酶和颗粒酶B切割位点的蛋白质列表中，这表明存在以前未被识别的保守基序。这两个切割位点都包含并保守在一个新的300个氨基酸的N末端结构域中，该结构域存在于小鼠和斑马鱼的明显UFD 2直系同源物中，但在低等真核生物的所有UFD 2家族成员中不存在。全长重组UFD 2在体外表现出泛素蛋白连接酶（'E3'）样的泛素化活性，但在颗粒酶B/caspase 6切割位点截短的重组UFD 2中这种活性被消除。UFD 2的切割半胱天冬酶或颗粒酶B在这个假定的调节N-末端结构域可能有重要的功能性后果的凋亡级联反应。
In the present study, we demonstrate that a human homologue of Ufd2p (a yeast protein that catalyses the formation of long polyubiquitin chains, and is implicated in responses to environmental stress), UFD2 (ubiquitin fusion degradation protein-2), is cleaved during apoptosis induced by multiple stimuli, including UVB irradiation, Fas ligation, staurosporine treatment and cytotoxic lymphocyte granule-induced death. Caspase 6 and granzyme B efficiently cleave UFD2 [kcat/Km= (4–5)×104M−1·s−1] at Asp123, whereas caspases 3 and 7 cleave UFD2 approx. 10-fold less efficiently immediately upstream at Asp109. Thus UFD2 is added to the growing list of proteins with closely spaced caspase and granzyme B cleavage sites, suggesting the presence of a previously unrecognized, conserved motif. Both cleavage sites are contained and conserved within a novel 300-amino-acid N-terminal domain present in apparent UFD2 orthologues in mice and zebrafish, but absent in all UFD2 family members in lower eukaryotes. Full-length recombinant UFD2 exhibited ubiquitin—protein ligase ('E3')-like ubiquitination activityin vitro, but this activity was abolished in recombinant UFD2 truncated at the granzyme B/caspase 6 cleavage site. Cleavage of UFD2 by caspases or granzyme B within this putative regulatory N-terminal domain might have important functional consequences within the apoptotic cascade.
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影响因子：
3.5
作者：
Sanghavi, DM;Thelen, M;Rosen, A
通讯作者：
Rosen, A
影响因子：
7
作者：
D. Vaux;R. Flavell
通讯作者：
D. Vaux;R. Flavell
Granzyme B的切割是对自身抗原状态的强烈预测：对自身免疫的影响。
影响因子：
15.3
作者：
Casciola-Rosen, L;Andrade, F;Ulanet, D;Wong, W B;Rosen, A
通讯作者：
Rosen, A
Fas 连接的 Jurkat 细胞中三种不同 ICE 样活性的依次激活
影响因子：
3.5
作者：
E. Greidinger;Douglas K. Miller;T. Yamin;L. Casciola;A. Rosen
通讯作者：
A. Rosen
影响因子：
32.4
作者：
Andrade, F;Roy, S;Casciola-Rosen, L
通讯作者：
Casciola-Rosen, L