tailieunhanh - Báo cáo khoa học: The myostatin-induced E3 ubiquitin ligase RNF13 negatively regulates the proliferation of chicken myoblasts

The ubiquitin ligase RING finger protein 13 gene (RNF13) was first identi-fied in a screen for genes whose expression is regulated by myostatin in chicken fetal myoblasts. In this study, we demonstrate that theRNF13gene is broadly expressed in many chicken tissues. | The myostatin-induced E3 ubiquitin ligase RNF13 negatively regulates the proliferation of chicken myoblasts Qiang Zhang1 Kun Wang2 Yong Zhang1 Jiao Meng1 Fang Yu2 Yan Chen2 and Dahai Zhu1 1 NationalLaboratory of MedicalMolecular Biology Department of Biochemistry and Molecular Biology Institute of Basic MedicalSciences Chinese Academy of MedicalSciences Peking Union MedicalCollege Beijing China 2 Molecular and Cellular DevelopmentalBiology Laboratory Harbin Institute of Technology China Keywords myoblast myostatin RNF13 skeletal muscle ubiquitin ligase Correspondence D. Zhu National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Peking Union MedicalCollege Tsinghua University 5 Dong Dan San Tiao Beijing 100005 China Fax 86 10 6510 5083 Tel 86 10 6529 6949 E-mail dhzhu@ These authors contributed equally to this work The ubiquitin ligase RING finger protein 13 gene RNF13 was first identified in a screen for genes whose expression is regulated by myostatin in chicken fetal myoblasts. In this study we demonstrate that the RNF13 gene is broadly expressed in many chicken tissues. The expression of RNF13 gradually decreases during skeletal myogenesis and myostatin up-regulates RNF13 expression at both the transcriptional and translational levels. Interestingly ectopic expression of RNF13 inhibits cell proliferation and suppresses the expression of the myogenic genes MyoD and Caveolin-3 in muscle cells. Moreover recently we have reported that RNF13 is a RINGtype E3 ubiquitin ligase. In this report we provide experimental evidence to show that mutations disrupting the RING finger abolish the growthsuppressive activity of RNF13 indicating that its E3 ligase activity is required for the inhibition of cell proliferation. Taken together our findings show that RNF13 functions as an E3 ubiquitin ligase to negatively regulate cell proliferation. Received 24 September 2009 revised 14 November 2009 accepted