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Publication : ZKSCAN3 is a master transcriptional repressor of autophagy.

First Author  Chauhan S Year  2013
Journal  Mol Cell Volume  50
Issue  1 Pages  16-28
PubMed ID  23434374 Mgi Jnum  J:203505
Mgi Id  MGI:5527132 Doi  10.1016/j.molcel.2013.01.024
Citation  Chauhan S, et al. (2013) ZKSCAN3 is a master transcriptional repressor of autophagy. Mol Cell 50(1):16-28
abstractText  Autophagy constitutes a major cell-protective mechanism that eliminates damaged components and maintains energy homeostasis via recycling nutrients under normal/stressed conditions. Although the core components of autophagy have been well studied, regulation of autophagy at the transcriptional level is poorly understood. Herein, we establish ZKSCAN3, a zinc finger family DNA-binding protein, as a transcriptional repressor of autophagy. Silencing of ZKSCAN3 induced autophagy and increased lysosome biogenesis. Importantly, we show that ZKSCAN3 represses transcription of a large gene set (>60) integral to, or regulatory for, autophagy and lysosome biogenesis/function and that a subset of these genes, including Map1lC3b and Wipi2, represent direct targets. Interestingly, ZKSCAN3 and TFEB are oppositely regulated by starvation and in turn oppositely regulate lysosomal biogenesis and autophagy, suggesting that they act in conjunction. Altogether, our study uncovers an autophagy master switch regulating the expression of a transcriptional network of genes integral to autophagy and lysosome biogenesis/function.
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