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CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases

  • Pu Wang
  • Junbin Song
  • Dan YeEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1217)

Abstract

The ubiquitin proteasome pathway is one of the major regulatory tools used by eukaryotic cells. The evolutionarily conserved cullin family proteins can assemble as many as >600 distinct E3 ubiquitin ligase complexes that regulate diverse cellular pathways. In most of Cullin-RING ubiquitin ligase (CRL) complexes, separate linker and adaptor proteins build the substrate recognition module. Differently, a single BTB-containing adaptor molecule utilizing two protein interaction sites can link the CUL3 scaffold to the substrate, forming as many as 188 CUL3-BTB E3 ligase complexes in mammals. Here, we review the most recent studies on CRL3 complexes, with a focus on the model for CUL3 assembly with its BTB-containing substrate receptors. Also, we summarize the current knowledge of CRL3 substrates and their relevant biological functions. Next, we discuss the mutual exclusivity of somatic mutations in KEAP1, NRF2, and CUL3 in human lung cancer. Finally, we highlight new strategies to expand CUL3 substrates and discuss outstanding questions remaining in the field.

Keywords

CRL3 BTB NRF2-KEAP1-CUL3 Lung cancer 

Abbreviations

AID

Auxin-induced degradation

ANKFY1

Ankyrin repeat and FYVE domain-containing 1

APC

Anaphase-promoting complex

ARE

The antioxidant response element

ATF2

Activating transcription factor 2

BCL2

B-cell CLL/lymphoma 2

BTB

Bric-à-brac, tramtrack and broad

BTB-ZF

BTB-zinc finger

bTRCP

Beta-transducin repeat-containing E3 ubiquitin protein ligase

CENP-A

Centromere protein A

CRL

Cullin-RING ubiquitin ligase

CRN7

Coronin 7

CUL

Cullin

DDB1

Damage-specific DNA binding protein 1

DWD

DDB1-binding WD40

eEF1A1

Eukaryotic translation elongation factor 1 alpha 1

EPS15

Epidermal growth factor receptor pathway substrate 15

ESCRT

Endosomal sorting complexes required for transport

FHIT

Fragile histidine triad gene

GSTA2

Glutathione S-transferase A2

HECT

Homologous to the E6-AP Carboxyl Terminus

IVR

Intervening region

Keap1

Kelch ECH associating protein 1

KLHDC

Kelch domain-containing protein

KLHL

The Kelch-like

LUSC

Lung squamous cell carcinomas

MEI-1

Meiosis inhibitor protein 1

MVBs

Multivesicular bodies

NEDD8

Neural precursor cell expressed, developmentally downregulated 8

NFE2

Nuclear factor, erythroid 2

NGS

Next-generation sequencing

NQO1

NADPH:quinone oxidoreductase 1

Nrf1

Nuclear respiratory factor 1

NRF2

Nuclear factor erythroid 2-related factor 2

NSCLC

Non-small cell lung cancer

p16 INK4a

Cyclin-dependent kinase inhibitor 2A

PLK1

Polo-like kinases 1

Rb1

Retinoblastoma 1

RBR

RING-In between-RING

RDX

Radixin

RING

Really Interesting New Gene

ROS

Reactive oxygen species

SCF

SKP1-CUL1-F-box

SEC31

Secretory 31

SKP1

S-Phase kinase associated protein 1

SOCS

Suppressor of cytokine signaling

SPOP

Speckle type BTB/POZ protein

SPOPL

Speckle type BTB/POZ protein like

TGN

Trans-Golgi network

ULK1

Unc-51 like autophagy activating kinase 1

WES

Whole-exome sequencing

WNK4

WNK lysine deficient protein kinase 4

Notes

Acknowledgments

This work was supported by the National Key R&D Program of China (No.2016YFA0501800 to D.Y.) and the NSFC grant (No. 31871431, No. 81522033, No. 31821002 to D. Y.).

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Molecular and Cell Biology LabInstitutes of Biomedical Sciences, Shanghai Medical College, Fudan UniversityShanghaiChina

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