Wang Y, Guan X, Fok K L, Li S, Zhang X, Miao S, Zong S, Koide S S, Chan H C, Wang L
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University 5 Dong Dan San Tiao, Beijing, 100005, China.
Cell Mol Life Sci. 2008 Nov;65(23):3822-9. doi: 10.1007/s00018-008-8452-0.
Rhomboid family members are widely conserved and found in all three kingdoms of life. They are serine proteases and serve important regulatory functions. In the present study, a novel gene highly expressed in the testis, RHBDD1, is shown to be a new member of the Rhomboid family, participating in the cleavage of BIK, a proapoptotic member of the Bcl-2 family. The RHBDD1-involved proteolytic modification is upstream of the BIK protein degradation pathway. Mutagenesis studies show that the amino acid residues glycine142 and serine144 of RHBDD1 are crucial for its activity in cleaving BIK at a site located in the transmembrane region. Overexpression or knock-down of RHBDD1 in HEK 293T cells can reduce or enhance BIK-mediated apoptosis, respectively. The present findings suggest that, by acting as a serine protease, RHBDD1 modulates BIK-mediated apoptotic activity.
类菱形蛋白酶家族成员广泛存在且在生命的三个王国中均有发现。它们是丝氨酸蛋白酶并发挥重要的调节功能。在本研究中，一个在睾丸中高表达的新基因RHBDD1被证明是类菱形蛋白酶家族的新成员，参与Bcl-2家族促凋亡成员BIK的裂解。涉及RHBDD1的蛋白水解修饰位于BIK蛋白降解途径的上游。诱变研究表明，RHBDD1的甘氨酸142和丝氨酸144氨基酸残基对于其在跨膜区域的一个位点裂解BIK的活性至关重要。在HEK 293T细胞中过表达或敲低RHBDD1可分别降低或增强BIK介导的细胞凋亡。本研究结果表明，作为一种丝氨酸蛋白酶，RHBDD1调节BIK介导的凋亡活性。
