VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma-Reference-Cited by-同舟云学术

VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Published:2018-07-20 Issue:6399 Volume:361 Page:290-295
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Zhang Jing¹²^ORCID,Wu Tao³^ORCID,Simon Jeremy¹⁴^ORCID,Takada Mamoru¹^ORCID,Saito Ryoichi¹,Fan Cheng¹,Liu Xian-De⁵^ORCID,Jonasch Eric⁵^ORCID,Xie Ling⁶,Chen Xian⁶,Yao Xiaosai⁷⁸^ORCID,Teh Bin Tean⁸⁹¹⁰^ORCID,Tan Patrick⁷¹⁰,Zheng Xingnan¹^ORCID,Li Mingjie¹^ORCID,Lawrence Cortney¹,Fan Jie¹¹^ORCID,Geng Jiang¹²^ORCID,Liu Xijuan¹,Hu Lianxin¹,Wang Jun¹,Liao Chengheng¹,Hong Kai¹,Zurlo Giada¹,Parker Joel S.¹^ORCID,Auman J. Todd¹^ORCID,Perou Charles M.¹^ORCID,Rathmell W. Kimryn¹³^ORCID,Kim William Y.¹,Kirschner Marc W.³^ORCID,Kaelin William G.¹⁴^ORCID,Baldwin Albert S.¹^ORCID,Zhang Qing¹²¹⁵^ORCID

Affiliation:

1. Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

2. Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.

3. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

4. Department of Genetics, Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.

5. Departments of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

6. Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.

7. Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore 138672, Singapore.

8. Institute of Molecular and Cell Biology, Singapore 138673, Singapore.

9. Laboratory of Cancer Epigenome, Department of Medical Sciences, National Cancer Centre, Singapore 169610, Singapore.

10. Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore.

11. Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China.

12. Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.

13. Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

14. Howard Hughes Medical Institute, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

15. Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.

Abstract

Mechanistic insights into kidney cancer Many clear cell renal cell carcinomas (ccRCCs) have alterations to the gene encoding the von Hippel-Lindau protein (VHL). VHL is a ubiquitin ligase that degrades target proteins when they are prolyl-hydroxylated. Zhang et al. performed a genome-wide search for VHL target (see the Perspective by Sanchez and Simon). They identified ZHX2, a protein with structural motifs that indicate DNA binding. ZHX2 has been implicated in tumor suppression. Loss of ZHX2 inhibited signaling through the transcription factor NF-κB, and ZHX2 bound to many NF-κB target genes. Depletion of ZHX2 slowed growth of ccRCC cells in vitro and in a mouse model. Science , this issue p. 290 ; see also p. 226

Funder

U.S. Department of Defense

National Cancer Institute

Korea National Institute of Health

National Institute of Health

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference52 articles.

1. Renal cell carcinoma

2. Integrated molecular analysis of clear-cell renal cell carcinoma