The E3 ligase APC/CCdh1 promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth

Juxiang Cao; Xiangpeng Dai; Lixin Wan; Hongshen Wang; Jinfang Zhang; Philip S. Goff; Elena V. Sviderskaya; Zhenyu Xuan; Zhixiang Xu; Xiaowei Xu; Philip Hinds; Keith T. Flaherty; Douglas V. Faller; Colin R. Goding; Yongjun Wang; Wenyi Wei; Rutao Cui

doi:10.1126/scisignal.aab1995

Research ArticleCancer

The E3 ligase APC/C^Cdh1 promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth

Juxiang Cao¹,*,†,
Xiangpeng Dai²,*,
Lixin Wan²,*,
Hongshen Wang¹,³,
Jinfang Zhang²,
Philip S. Goff⁴,
Elena V. Sviderskaya⁴,‡,
Zhenyu Xuan⁵,
Zhixiang Xu⁶,
Xiaowei Xu⁷,
Philip Hinds⁸,
Keith T. Flaherty⁹,
Douglas V. Faller¹⁰,
Colin R. Goding¹¹,
Yongjun Wang³,§,
Wenyi Wei²,§, and
Rutao Cui¹,³,§

¹Department of Pharmacology and Experimental Therapeutics, Boston University Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA.
²Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
³Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 20032, P. R. China.
⁴Molecular Cell Sciences Research Centre, Canadian Cancer Society Research Institute, St. George’s, University of London, Cranmer Terrace, London SW17 0RE, UK.
⁵Department of Molecular and Cell Biology, The University of Texas at Dallas, Dallas, TX 75080, USA.
⁶Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35233, USA.
⁷Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁸Department of Developmental, Molecular and Chemical Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
⁹Cancer Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.
¹⁰Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA.
¹¹Ludwig Institute for Cancer Research, University of Oxford, Headington, Oxford OX3 7DQ, UK.

↵§Corresponding author. E-mail: yjwang88{at}hotmail.com (Y.W.); wwei{at}bidmc.harvard.edu (W.W.); rutaocui{at}bu.edu (R.C.)

↵* These authors contributed equally to this work.
↵† Present address: Division of Pulmonary and Critical Care Medicine and of Genetics, Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.
↵‡ Present address: Molecular Cell Sciences Research Centre, St. George’s, University of London, London SW17 0RE, UK.

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Science Signaling 01 Sep 2015:
Vol. 8, Issue 392, pp. ra87
DOI: 10.1126/scisignal.aab1995

Juxiang Cao

1Department of Pharmacology and Experimental Therapeutics, Boston University Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA.

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Xiangpeng Dai

2Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

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Lixin Wan

2Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

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Hongshen Wang

1Department of Pharmacology and Experimental Therapeutics, Boston University Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA.

3Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 20032, P. R. China.

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Jinfang Zhang

2Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

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Philip S. Goff

4Molecular Cell Sciences Research Centre, Canadian Cancer Society Research Institute, St. George’s, University of London, Cranmer Terrace, London SW17 0RE, UK.

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Elena V. Sviderskaya

4Molecular Cell Sciences Research Centre, Canadian Cancer Society Research Institute, St. George’s, University of London, Cranmer Terrace, London SW17 0RE, UK.

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Zhenyu Xuan

5Department of Molecular and Cell Biology, The University of Texas at Dallas, Dallas, TX 75080, USA.

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Zhixiang Xu

6Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35233, USA.

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Xiaowei Xu

7Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Philip Hinds

8Department of Developmental, Molecular and Chemical Biology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.

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Keith T. Flaherty

9Cancer Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.

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Douglas V. Faller

10Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA.

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Colin R. Goding

11Ludwig Institute for Cancer Research, University of Oxford, Headington, Oxford OX3 7DQ, UK.

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Yongjun Wang

3Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 20032, P. R. China.

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For correspondence: yjwang88@hotmail.com wwei@bidmc.harvard.edu rutaocui@bu.edu

Wenyi Wei

2Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

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For correspondence: yjwang88@hotmail.com wwei@bidmc.harvard.edu rutaocui@bu.edu

Rutao Cui

1Department of Pharmacology and Experimental Therapeutics, Boston University Cancer Center, Boston University School of Medicine, Boston, MA 02118, USA.

3Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 20032, P. R. China.

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For correspondence: yjwang88@hotmail.com wwei@bidmc.harvard.edu rutaocui@bu.edu

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The E3 ligase APC/C^Cdh1 promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth

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