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The role of E3 ubiquitin ligase HECTD3 in cancer and beyond

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Abstract

Ubiquitin modification plays significant roles in protein fate determination, signaling transduction, and cellular processes. Over the past 2 decades, the number of studies on ubiquitination has demonstrated explosive growth. E3 ubiquitin ligases are the key enzymes that determine the substrate specificity and are involved in cancer. Several recent studies shed light on the functions and mechanisms of HECTD3 E3 ubiquitin ligase. This review describes the progress in the recent studies of HECTD3 in cancer and other diseases. We propose that HECTD3 is a potential biomarker and a therapeutic target, and discuss the future directions for HECTD3 investigations.

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Abbreviations

ACC:

Adrenocortical carcinoma

ANGPT1:

Angiopoietin 1

BRCA:

Breast invasive carcinoma

BRCA1:

Breast cancer type 1 susceptibility protein

c-Abl:

Abelson murine leukemia viral homolog 1

CHOL:

Cholangiocarcinoma

CRAF:

RAF proto-oncogene serine/threonine-protein kinase

CRL7:

Cullin-RING E3 ubiquitin ligase 7

CUL1:

Cullin1

CUL7:

Cullin 7

DECL:

DNA-encoded compound libraries

DISC:

Death-inducing signaling complex

DLBC:

Lymphoid neoplasm diffuse large B-cell lymphoma

DUB:

Deubiquitinating enzyme

E1:

Ubiquitin-activating enzyme

E2:

Ubiquitin-conjugating enzyme

E3:

Ubiquitin ligase

E6-AP:

E6-associated protein

EAE:

Experimental autoimmune encephalomyelitis

ECT2:

Epithelial cell transforming 2

EGFR:

Epidermal growth factor receptor

ER:

Endoplasmic reticulum

ERBB4:

Erb-b2 receptor tyrosine kinase 4

ERK:

Mitogen-activated protein kinase 1

ESCC:

Esophageal squamous cell carcinoma

FBDD:

Fragment-based drug discovery

FBW7:

F-box and WD repeat domain containing 7

FP-HTS:

Fluorescence polarization assay for high-throughput screening

HECT:

Homologous to E6AP C terminus

HECTD3:

Homologous to the E6-associated protein carboxyl terminus domain containing 3

HER2:

Erb-b2 receptor tyrosine kinase 2

HIF1α:

Hypoxia inducible factor 1 subunit alpha

HSP90:

Heat shock protein 90

HTS:

High-throughput screening technologies

HUWE1:

HECT, UBA, and WWE domain containing E3 ubiquitin protein ligase 1

IFN:

Interferon

IRE1α:

Inositol requiring enzyme 1 alpha

IRF3:

Interferon regulatory factor 3

ITCH:

Itchy E3 ubiquitin protein ligase

KLF5:

Kruppel like factor 5

LATS1:

Large tumor suppressor kinase 1

LIHC:

Liver hepatocellular carcinoma

LGG:

Brain lower grade glioma

LUAD:

Lung adenocarcinoma

MALT1:

MALT1 paracaspase

MCL1:

Myeloid cell leukemia 1

MDM2:

Murine double minute 2

miR-153:

MicroRNA-153

NEDD4-1:

NEDD4 E3 ubiquitin protein ligase

OV:

Ovarian serous cystadenocarcinoma

PMA:

Phorbol-12-myristate-13-acetate

PML:

Promyelocytic leukemia protein

PTEN:

Phosphatase and tensin homolog

RBR:

RING-IBR-RINGs

RING:

Really interesting new genes

RLD:

RCC1 like domain

RNF20:

Ring finger protein 20

RORγt:

Retineic-acid-receptor-related orphan nuclear receptor γ

SCF:

SKP1-CUL1-F-box protein

SKP2:

S-phase kinase-associated protein 2

SMAD2:

SMAD family member 2

SMURF2:

SMAD specific E3 ubiquitin protein ligase 2

Stat3:

Signal transducer and activator of transcription 3

Tara:

Trio-associated repeat on actin

TBK1:

TANK binding kinase 1

TGFβ:

Transforming growth factor β

TGFβR1:

Transforming growth factor β receptor 1

Th17:

T helper 17

THCA:

Thyroid carcinoma

THYM:

Thymoma

TNBC:

Triple negative breast cancer

TRAF3:

TNF receptor-associated factor 3

TRAF6:

TNF receptor-associated factor 6

TRAIL:

TNF-related apoptosis-inducing ligand

Ub:

Ubiquitin

UCEC:

Uterine Corpus Endometrial Carcinoma

UCS:

Uterine Carcinosarcoma

UbV:

Ub variant

UCS:

Uterine carcinosarcoma

VCB-CR:

pVHL-elongin C-elongin B-cullin 2-RBX1

VHL:

Von Hippel–Lindau disease tumor suppressor

WWP1:

WW domain containing E3 ubiquitin protein ligase 1

WWP2:

WW domain containing E3 ubiquitin protein ligase 2

XBP1:

X-box binding protein 1

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Acknowledgements

This study was supported in part by grants from the National Key R&D Program of China (2018YFC2000400) and the National Nature Science Foundation of China (81830087, U1602221, and 31771516 to Chen, C and 81773149 to Kong Y) and the Shenzhen Municipal Government of China (KQTD20170810160226082).

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  1. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China

    Qiuyun Jiang, Zhuo Cheng & Ceshi Chen

  2. Kunming College of Life Science, University of the Chinese Academy of Sciences, Kunming, 650204, China

    Qiuyun Jiang, Zhuo Cheng & Ceshi Chen

  3. Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, 510095, China

    Fubing Li

  4. Institute of Translation Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China

    Yanjie Kong

  5. KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China

    Ceshi Chen

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Jiang, Q., Li, F., Cheng, Z. et al. The role of E3 ubiquitin ligase HECTD3 in cancer and beyond. Cell. Mol. Life Sci. 77, 1483–1495 (2020). https://doi.org/10.1007/s00018-019-03339-3

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