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

• Published in: Acta biochimica et biophysica Sinica 2014-08, Vol.46 (8), p.668-674
• Main Authors: Zhao, Yuanbo, Hongdu, Beiqi, Ma, Dalong, Chen, Yingyu
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Apoptosis; Base Sequence; Caenorhabditis elegans; Caspase; Cell Line, Tumor; Gene Knockdown Techniques; Golgi Apparatus - metabolism; Humans; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - physiology; Molecular Sequence Data; Reverse Transcriptase Polymerase Chain Reaction; RING; 人类基因组; 定位; 细胞凋亡; 胱天蛋白酶-3; 膜蛋白; 高尔基体
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmu047

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.