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The Roles of Cullin-2 E3 Ubiquitin Ligase Complex in Cancer

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Cullin-RING Ligases and Protein Neddylation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1217))

Abstract

Posttranslational protein modifications play an important role in regulating protein stability and cellular function. There are at least eight Cullin family members. Among them, Cullin-2 forms a functional E3 ligase complex with elongin B, elongin C, RING-box protein 1 (RBX1, also called ROC1), as well as the substrate recognition subunit (SRS) to promote the substrate ubiquitination and degradation. In this book chapter, we will review Cullin-2 E3 ligase complexes that include various SRS proteins, including von Hippel Lindau (pVHL), leucine-rich repeat protein-1 (LRR-1), preferentially expressed antigen of melanoma (PRAME), sex-determining protein FEM-1 and early embryogenesis protein ZYG-11. We will focus on the VHL signaling pathway in clear cell renal cell carcinoma (ccRCC), which may reveal various therapeutic avenues in treating this lethal cancer.

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Abbreviations

Ankrd37:

Ankyrin repeat domain 37

APC/C:

Anaphase-promoting complex/cyclosome

ARNT:

Aryl hydrocarbon receptor nuclear translocator

ccRCC:

Clear cell renal cell carcinoma

ChIP-Seq:

ChIP assays followed by deep sequencing

CKI:

Cip/Kip CDK-inhibitor

COL4α2:

Collagen IV alpha 2

CRL:

Cullin-based ringlike

ECM:

Extracellular matrix

EglNs:

Egl nine homologs

GLUT1:

Glucose uptake and metabolism

HREs:

Hypoxia-responsive elements

LRR-1:

Leucine-rich repeat protein-1

MDM2:

Double minute 2 homolog

PD1:

Programmed cell death protein 1

PDL1:

Programmed cell death protein 1 ligand 1

PI3K:

Phosphoinositide 3-kinase

PKB:

Protein kinase B

PRAME:

Preferentially expressed antigen of melanoma

pVHL:

Von Hippel–Lindau protein

RBX1:

RING-box protein 1

SRS:

Substrate recognition subunit

ZHX2:

Zinc fingers and homeoboxes 2

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Authors and Affiliations

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

    Xijuan Liu, Giada Zurlo & Qing Zhang

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

    Qing Zhang

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

    Qing Zhang

  4. Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA

    Giada Zurlo & Qing Zhang

Authors
  1. Xijuan Liu
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  2. Giada Zurlo
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  3. Qing Zhang
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Correspondence to Qing Zhang .

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Editors and Affiliations

  1. Radiation Oncology, University of Michigan, Ann Arbor, MI, USA

    Yi Sun

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

    Wenyi Wei

  3. Life Science Institute, Zhejiang University, Hangzhou, China

    Jianping Jin

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Liu, X., Zurlo, G., Zhang, Q. (2020). The Roles of Cullin-2 E3 Ubiquitin Ligase Complex in Cancer. In: Sun, Y., Wei, W., Jin, J. (eds) Cullin-RING Ligases and Protein Neddylation. Advances in Experimental Medicine and Biology, vol 1217. Springer, Singapore. https://doi.org/10.1007/978-981-15-1025-0_11

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