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Ubiquitin carboxyl-terminal hydrolases: involvement in cancer progression and clinical implications

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Abstract

Protein ubiquitination and deubiquitination participate in a number of biological processes, including cell growth, differentiation, transcriptional regulation, and oncogenesis. Ubiquitin C-terminal hydrolases (UCHs), a subfamily of deubiquitinating enzymes (DUBs), includes four members: UCH-L1/PGP9.5 (protein gene product 9.5), UCH-L3, UCHL5/UCH37, and BRCA1-associated protein-1 (BAP1). Recently, more attention has been paid to the relationship between the UCH family and malignancies, which play different roles in the progression of different tumors. It remains controversial whether UCHL1 is a tumor promoter or suppressor. UCHL3 and UCH37 are considered to be tumor promoters, while BAP1 is considered to be a tumor suppressor. Studies have showed that UCH enzymes influence several signaling pathways that play crucial roles in oncogenesis, tumor invasion, and migration. In addition, UCH families are associated with tumor cell sensitivity to therapeutic modalities. Here, we reviewed the roles of UCH enzymes in the development of tumors, highlighting the potential consideration of UCH enzymes as new interesting targets for the development of anticancer drugs.

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Abbreviations

Aβ:

Amyloid-β peptides

AD:

Alzheimer’s disease

BAP1:

BRCA1-associated protein-1

BARD1:

BRCA1-associated RING domain 1

CDCA2:

Cell division cycle-associated 2

CG:

Cortical granule

CKD:

Cyclin-dependent kinases

DDR:

DNA damage response

DFS:

Disease-free survival

di-Ub:

Dimers-ubiquitin

DSBs:

Double-strand breaks

DUBs:

Deubiquitinating enzymes

E2F1:

E2 promoter binding factor 1

EMT:

Epithelial-to-mesenchymal transition

EOC:

Epithelial ovarian cancer

ESCC:

Esophageal squamous cell carcinoma

gad:

Gracile axonal dystrophy

GRP78:

Glucose-regulated protein 78

HBM:

HCF1 binding domain

HCC:

Hepatocellular carcinoma

HCF1:

Host cell factor 1

HDAC:

Histone deacetylase

HIF-1:

Hypoxia-inducible factor 1

hINO80:

Human Ino80 chromatin-remodeling complex

HR:

Proper homologous recombination

IFI27:

Interferon inducible protein 27

JAB1:

Jun activation domain-binding protein-1

JAMM:

Jab1/MPN domain-associated metalloisopeptidase

MJDs:

Josephin or Machado-Joseph disease protein domain proteases

mono-Ub:

Mono-ubiquitin

NF-κB:

Nuclear factor-κB

NFRKB:

Nuclear factor related to κB

NLS:

Nuclear localization signals

NOX4:

NADPH oxidase 4

OGT:

O-linked N-acetylglucosamine transferase

OS:

Overall survival

OTUs:

Ovarian tumor proteases

PD:

Parkinson’s disease

PGP9.5:

Protein gene product 9.5

PRCs:

Polycomb-repressive complexes

PR-DUB:

Polycomb group repressive deubiquitinase complex

RCC:

Renal clear cell carcinoma

ROS:

Reactive oxygen species

Smurf2:

Smad ubiquitination regulatory factor 2

TGF-β:

Transforming growth factor-β

Ub:

Ubiquitin

UCHs:

Ubiquitin C-terminal hydrolases

UPP:

Ubiquitin-dependent proteasome degradation pathway

USPs/UBPs:

Ubiquitin-specific proteases/ubiquitin-specific processing proteases

YY1:

Ying Yang 1

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Acknowledgements

This study was financially supported by grants from the National Nature Science Foundation of China (Nos. 81301820, 81472673, 81672720, 81672334), the Fund of Shanghai Science and Technology Commission (16ZR1406100) and the National Clinical Key Special Subject of China.

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Authors and Affiliations

  1. The Department of Gastroenterology of Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, People’s Republic of China

    Ying Fang & Xizhong Shen

  2. Key Laboratory of Medical Molecule Virology, Ministry of Education and Health, Shanghai Institute of Liver Diseases Fudan University, Shanghai, 200032, People’s Republic of China

    Xizhong Shen

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  1. Ying Fang
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  2. Xizhong Shen
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Correspondence to Xizhong Shen.

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Fang, Y., Shen, X. Ubiquitin carboxyl-terminal hydrolases: involvement in cancer progression and clinical implications. Cancer Metastasis Rev 36, 669–682 (2017). https://doi.org/10.1007/s10555-017-9702-0

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  • DOI: https://doi.org/10.1007/s10555-017-9702-0

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