title: DHRSX, a novel non-classical secretory protein associated with starvation induced autophagy.
abstract: Dehydrogenase/reductase (SDR family) X-linked (DHRSX) is a novel human gene without any substantial functional annotation and was initially cloned and identified in our laboratory. In this study, we present evidence that it encodes a non-classical secretory protein and promotes starvation induced autophagy. Using the Baf.A1 assay and N-terminal sequencing, we showed that DHRSX is secreted in a non-classical form. We expressed and purified a recombinant human GST-DHRSX fusion protein. Functional studies revealed that HeLa and U2OS cells overexpressing DHRSX or treated with the GST-DHRSX fusion protein exhibited higher levels of starvation-induced autophagy, resulting in increased endogenous LC3-II levels, a punctate GFP-LC3 distribution, and structures associated with autophagy, with a lower accumulation of autophagy substrates such as p62 and polyQ80. Accordingly, knockdown of endogenous DHRSX through specific siRNAs reduced LC3-II levels obviously in U2OS cells induced by starvation. Collectively, these results demonstrate that DHRSX is a novel non-classical secretory protein involved in the positive regulation of starvation induced autophagy and provide a new avenue for research on this protein family and autophagy regulation.
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Guoying
authors: G
authors: Zhang
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Yang
authors: Y
authors: Luo
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Ge
authors: G
authors: Li
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Lanlan
authors: L
authors: Wang
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Daxiang
authors: D
authors: Na
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Xiaotong
authors: X
authors: Wu
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Yingmei
authors: Y
authors: Zhang
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Xiaoning
authors: X
authors: Mo
authors: 1. Center for Human Disease Genomics, Department of Immunology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, P. R. China ; 2. Key Laboratory of Medical Immunology, Ministry of Health, School of Basic Medical Science, Peking University, Beijing 100191, P. R. China.
authors: Lu
authors: L
authors: Wang
mesh_terms: D001343:Autophagy / Q000235:genetics*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013217:Starvation / Q000201:enzymology* / Q000235:genetics
chemical_list: D049452:Green Fluorescent Proteins; D010088:Oxidoreductases; C022690:succinic-dichloroindophenol reductase
keywords: Autophagy; DHRSX; Non-classical secretory protein; Novel gene