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Physiological functions and clinical implications of the N-end rule pathway

Frontiers of Medicine 2016年第3期10卷 258-270页

作者： Yujiao Liu Chao Liu Wen Dong Wei Li College of Marine Life Ocean University of China Qingdao 266003 China State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China

The N-end rule pathway is a unique branch of the ubiquitin-proteasome system in which the determination of a protein＇s half-life is dependent on its N-terminal residue. The N-terminal residue serves as the degradation signal of a protein and thus called N-degron. N-degron can be recognized and modifed by several steps of post-translational modifications, such as oxidation, deamination, arginylation or acetylation, it then polyubiquitinated by the N-recognin for degradation. The molecular basis of the N-end rule pathway has been elucidated and its physiological functions have been revealed in the past 30 years. This pathway is involved in several biological aspects, including transcription, differentiation, chromosomal segregation, genome stability, apoptosis, mitochondrial quality control, cardiovascular development, neurogenesis, carcinogenesis, and spermatogenesis. Disturbance of this pathway often causes the failure of these processes, resulting in some human diseases. This review summarized the physiological functions of the N-end rule pathway, introduced the related biological processes and diseases, with an emphasis on the inner link between this pathway and certain symptoms.

关键词： N-end rule pathway Ate l cardiovascular development neurogenesis spermatogenesis neurodegenerativedisorders Johanson-Blizzard syndrome

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Retroviral Insertional Mutagenesis Screen for Genes Involved in Human Disease Modeling in Zebrafish

Retroviral Insertional Mutagenesis Screen for Genes Involved...

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“基因、进化与生理功能多样性”海内外学术研讨会暨中国生理学会第七届比较生理学学术会议

作者： Ying Zhang~1,Nai-Zhong Zheng~1,Shuo Lin~(1,2),Bo Zhang~1 1 Key Laboratory of Cell Proliferation and Differentiation,Center of developmental Biology and Genetics,College of Life Sciences,Peking University,Ministry of Education,Beijing 2 Department of Molecular,Cell & developmental Biology,University of California,Los Angeles, Los Angeles,CA 90095-1606,USA

Through retrovirus insertion based mutagenesis screen in zebrafish（Danio reiro） we have obtained several insertions that reside in *** and WDR55 are two candidate genes we conducted further *** encodes a cytokine induced anti-apoptosis protein with a methyltransferase domain, whose ortholog in mice is called Anamorsin. Ciapinl/Anamorsin represents a novel antiapoptotic protein that shares no homology with Bcl-2 and Capase family *** mouse embryos has been reported to be smaller in size compared with wild type littermates, show defects in definitive hemato-poiesis in fetal livers,and begin to die between E12.5 and *** mount in situ hybridization in zebrafish embryos revealed a broad expression pattern of *** ciapinl embryos exhibits edema in pericardial ***55 is a member of WDR-containing protein *** studies have shown that PeBoW complex,which contains a component of WDR12,is required for matura- tion of 60S ribosomal *** is also reported that WDR55 is involved in rRNA processing and cell *** data showed that WDR55 zebrafish embryos begin to die between 7 days post fertilization（dpf） and 10 *** mount in situ hybridization with markers of hematopoietic stem cells c-myb and runxl showed decreased expression in WDR55 *** may imply a function of WDR55 in definitive *** study is interesting because ribosome deficiency has been implicated in several human diseases such as Diamond-Blackfan Anemia that has congenital erythroid *** zebrafish mutants might be useful for modeling and understanding pathogenesis of these human diseases.

关键词： Zebrafish Insertional mutagenesis Retrovirus cardiovascular development

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