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The Putative Cancer Stem Cell Marker USP22 Is a Subunit of the Human SAGA Complex Required for Activated Transcription and Cell-Cycle Progression
Xiao-Yong Zhang,1,5 Maya Varthi,1,5 Stephen M. Sykes,2 Charles Phillips,1 Claude Warzecha,2 Wenting Zhu,2 Anastasia Wyce,2 Alan W. Thorne,3 Shelley L. Berger,4 and Steven B. McMahon1,
1 The Department of Cancer Biology, The Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA
2 The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
3 University of Portsmouth, Portsmouth PO1 2DT, UK
4 The Wistar Institute, Philadelphia, PA 19104, USA
Corresponding author
Steven B. McMahon
Polycomb genes encode critical regulators of both normal stem cells and cancer stem cells. A gene signature that includes Polycomb genes and additional genes coregulated with Polycomb genes was recently identified. The expression of this signature has been reported to identify tumors with the cancer stem cell phenotypes of aggressive growth, metastasis, and therapy resistance. Most members of this 11 gene signature encode proteins with well-defined roles in human cancer. However, the function of the signature member USP22 remains unknown. We report that USP22 is a previously uncharacterized subunit of the human SAGA transcriptional cofactor complex. Within SAGA, USP22 deubiquitylates histone H2B. Furthermore, USP22 is recruited to specific genes by activators such as the Myc oncoprotein, where it is required for transcription. In support of a functional role within the Polycomb/cancer stem cell signature, USP22 is required for appropriate progression through the cell cycle.
