Table 1.

Summary of UPS subunits involved in formation of cancer. Where known, specific cancer subtypes in which the alteration is involved are indicated [17, 18]

UPS subunit	Mutation or deregulation	Malignancy	References
E3	HDM2	Various	[19–24]
	Overexpression, loss of tumor suppressor function through p53
	FBW7	Leukemia, cholangiocarcinoma, gastrointestinal, and endometrial cancer	[25–34]
	Mutant, loss of tumor suppressor function through cyclin E, MYC, JUN, and Notch
	SKP2	Colorectal, breast, biliary tract, and prostate cancer. NSCLC	[35–42]
	Mutant, loss of tumor suppressor function through p27
	VHL	Lung cancer, clear-cell carcinoma, VHL disease	[43]
	Mutant, loss of tumor suppressor function through HIF
DUB	USP1	Fanconi anemia (leukemia risk factor)	[44]
	Mutations in FANCD2 DNA repair pathways
	USP2	Prostate cancer	[45]
	Stabilizes HDM2, facilitates malignant metabolic profile through fatty acid synthetase activation
	USP4	Adenocarcinoma, breast cancer	[46, 47]
	Interactions with retinoblastoma protein, SMAD4, and β-catenin
	USP8		[48]
	Regulates expression of EGFR
	USP9x	Leukemia, myeloma, lymphoma, and pancreatic cancer	[49–51]
	Stabilizes β-catenin, SMAD4, and BCL1 family protein MCL1
	USP15	Glioblastoma	[52]
	Stabilizes SMAD4
	USP18	Leukemia	[53]
	USP19		[54]
	Stabilize anti-apoptotic regulators c-IAP1 and c-IAP2
	USP28		[55]
	Stabilizes c-MYC
	USP7, USP2a, USP10	Prostate cancer	[56, 57]
	Stabilize p53
19S	USP14	Lung adenocarcinoma	[58, 59]
	Stabilization of various regulators including IκB and β-catenin
	POH1/Rpn11		[60]
	Stabilization of c-JUN
Other	Human papilloma virus onco-protein	Cervical, head-and-neck cancer	[61, 62]
	Viral particle that mimics E3 activity, altering stability of various substrates including p53 and MYC