• Guoying Zhang, Yang Luo, Ge Li, Lanlan Wang, Daxiang Na, Xiaotong Wu, Yingmei Zhang, Xiaoning Mo, and Lu Wang.
• 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.
• Int J Med Sci. 2014 Jan 1; 11 (9): 962-70.

AbstractDehydrogenase/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.

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