The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression

被引：402

作者：

Zhang, Xiao-Yong ^{[1
]}

Varthi, Maya ^{[1
]}

Sykes, Stephen M. ^{[2
]}

Phillips, Charles ^{[1
]}

Warzecha, Claude ^{[2
]}

Zhu, Wenting ^{[2
]}

Wyce, Anastasia ^{[2
]}

Thorne, Alan W. ^{[3
]}

Berger, Shelley L. ^{[4
]}

McMahon, Steven B. ^{[1
]}

机构：

[1] Thomas Jefferson Univ, Coll Med, Kimmer Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA

[2] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[3] Univ Portsmouth, Portsmouth PO1 2DT, Hants, England

[4] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA

来源：

MOLECULAR CELL | 2008年 / 29卷 / 01期

关键词：

D O I：

10.1016/j.molcel.2007.12.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：102 / 111

页数：10

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