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Table 1 Actions of USP28 on its potential substrates in cancers

From: Ubiquitin-specific protease 28: the decipherment of its dual roles in cancer development

Target of USP28

Function of USP28

The region and site involved

Results of the USP28 effects on the target

References

FBW7 (FBXW7)

Antagonizing its autocatalytic ubiquitination

–

Degradation of oncoproteins

[28]

c-Myc

Countering the ubiquitination mediated by FBW7

amino-terminus of FBW7;

p–c-Myc-T58

Promoting the cell cycle and glycolysis

[5, 29, 30]

MBI domain of MYC;

USP28 Cys171

Transactivating the SLUG promoter to enhance cancer stem-like traits

[6, 31]

c-Jun

Inhibiting the functions of FBW7, deubiquitinating and stabilizing c-Jun

–

Accelerating cell proliferation

[35]

NICD1

Repressing functions of FBW7, deubiquitinating NICD1

–

Strengthening Notch signaling and influencing the secretory fate determination of intestine

[35]

HIF-1α

Revising the destabilization caused by FBW7, and promoting its accumulation through c-Myc

Closely related to the GSK-3β phosphorylation sites

Expediting the angiogenesis

[25]

Cyclin E1

Loss of USP28 that contributes to the autoubiquitination of FBW7 and overexpression of USP28 can stabilize it

–

Promoting cell cycle progression

[34]

STAT3

Upregulating STAT3 and reversing the polyubiquitination mediated by FBW7

–

Promoting cellular growth

[33]

p53

Deubiquitination p53 through antagonizing MDM2

MDM2-catalyzed K48 ubiquitin chains

Inducing apoptosis

[26]

ΔNp63

Removing the K-48 linked ubiquitin chains independently of FBW7

MDM2-catalyzed K48 ubiquitin chains

Facilitating cell proliferation and maintaining identity of squamous cancer cells

[25]

LSD1

Deubiquitinating and stabilizing it

An amine oxidase domain of LSD1;

N-terminal region of USP28

Suppressing differentiation, promoting cell proliferation and metastasis

[9, 55]

CD44

Removing ubiquitin group from CD44 protein and enhancing its stabilization

–

Maintaining the stem cell-like properties and promoting invasion

[36]

H2A

Binding H2A and deubiquitinating it

ub-K119-H2A

Suppressing cell proliferation

[32]

Claspin

Deubiquitinating and stabilizing it

–

Maintaining cell cycle arrest and cell survival in response of DNA damage caused by chemotherapy

[37]

Snail

Stabilizing Snail

–

–

[82]

Lin28A

Extending the half-life of Lin28A and stabilizing it

–

Promoting cell viability, colony formation and invasion

[74]

ZNF304

Decreasing ubiquitination of it

–

Switching of many tumor suppressor genes

[47]

MDC1

Leading to its stabilization

–

Promoting rescue from damage or contributing to apoptosis

[7]

UCK1

Antagonizing its ubiquitination caused by KLHL2

K81 of UCK1

Giving rise to the chemotherapeutic resistance to 5’AZA

[27]

CHK2

Turning over its ubiquitination mediated by PIRH2

–

Enhancing the activation of G1/S and G2/M checkpoints

(141)

Plk3

Antagonizing the suppression function of SIAH2

–

Inhibiting carcinogenesis

[111]

FOXM1

Directly interacting with it and promoting its stabilization

–

Promoting cell proliferation and inhibiting apoptosis

[4]

  1. CD44 cluster of differentiation-44, CHK2 checkpoint kinase 2, FBW7 F-box and WD repeat domain-containing protein 7, FOXM1 Forkhead box M1, GSK-3 glycogen synthase kinase-3, HIF-1α hypoxia-inducible factor-1α, KLHL2 Kelch-like 2, LSD1 lysine specific demethylase 1, MB I MYC Box I, MDC1 mediator of DNA damage checkpoint 1, MDM2 mouse double minute 2 protein, NICD1 NOTCH1 intracellular domain, PIRH2 p53-induced RING-H2, Plk3 polo-like kinase 3, STAT3 signal transducer and activator of transcription 3, ub-K119-H2A ubiquitination at K119 of histone H2A, UCK1 uridine-cytidine kinase, USP28 ubiquitin-specific protease 28, ZNF304 zinc finger protein 304