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 | |
MBI domain of MYC; USP28 Cys171 | Transactivating the SLUG promoter to enhance cancer stem-like traits | |||
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 | |
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] |