Really interesting new gene finger protein 121 is a novel Golgi-localized membrane protein that regulates apoptosis  

作　　者：Yuanbo Zhao 

机构地区：[1]Key Laboratory of Medical Immunology, Ministry of Health, Peking University Health Science Center, Beijing 100191, China [2]peking University Center for Human Disease Genomics, Peking University, Beijing 100191, China

出　　处：《Acta Biochimica et Biophysica Sinica》2014年第8期668-674,共7页生物化学与生物物理学报（英文版）

摘　　要：Really interesting new gene （RING） finger proteins represent a large protein family in the human genome, and play crucial roles in physiological activities and cancer develop- ment. The biological functions of some RING finger proteins remain unknown. Here, we described the biological activity of a novel, human Golgi-localized RING finger protein 121 （RNF121）, the function of which is, thus far, unknown. Unlike the endoplasmic reticulum-iocalized RNF121 in Caenorhabditis elegans, human RNF121 is predominantly localized to the Golgi apparatus. RNF121 knockdown inhib- ited cell growth and induced apoptosis, which was accom- panied by caspase-3 activation and the cleavage of poly （adenosine diphosphate-ribose） polymerase. Z-VAD-FMK, a pan-caspase inhibitor, inhibited the RNF121 knockdown- induced apoptosis. Over-expression of wild-type RNF121, but not the RING domain mutants of RNF121, decreased RNF121 knockdown-induced apoptosis, indicating that the RING domain is required for RNF121-regulated apoptosis. Moreover, RNF121 knockdown enhanced etoposide-induced apoptosis. This is the first study to demonstrate that RNF121 is a novel regulator of apoptosis and provides a new potential target for cancer therapy.Really interesting new gene （RING） finger proteins represent a large protein family in the human genome, and play crucial roles in physiological activities and cancer develop- ment. The biological functions of some RING finger proteins remain unknown. Here, we described the biological activity of a novel, human Golgi-localized RING finger protein 121 （RNF121）, the function of which is, thus far, unknown. Unlike the endoplasmic reticulum-iocalized RNF121 in Caenorhabditis elegans, human RNF121 is predominantly localized to the Golgi apparatus. RNF121 knockdown inhib- ited cell growth and induced apoptosis, which was accom- panied by caspase-3 activation and the cleavage of poly （adenosine diphosphate-ribose） polymerase. Z-VAD-FMK, a pan-caspase inhibitor, inhibited the RNF121 knockdown- induced apoptosis. Over-expression of wild-type RNF121, but not the RING domain mutants of RNF121, decreased RNF121 knockdown-induced apoptosis, indicating that the RING domain is required for RNF121-regulated apoptosis. Moreover, RNF121 knockdown enhanced etoposide-induced apoptosis. This is the first study to demonstrate that RNF121 is a novel regulator of apoptosis and provides a new potential target for cancer therapy.

关 键 词：RING finger protein 121 APOPTOSIS RINGdomain Golgi apparatus 

分 类 号：Q987[生物学—遗传学] Q255[生物学—人类学]