Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery

Li, Jack; Liu, Sijin; Li, Shitao

doi:10.1186/s12964-023-01239-5

Cell Communication and Signaling

Table 2 Mechanisms underlying the role of linear ubiquitination in cancer

From: Mechanisms underlying linear ubiquitination and implications in tumorigenesis and drug discovery

Cancer type	Gene	Mechanism	Ref
Lymphoma	HOIP	Q584H and Q662L mutations of HOIP increase LUBAC activity and NF-κB signaling	[45]
Lymphoma	CARD11	Oncogenic CARD11 variants facilitate BCL10 linear ubiquitination by co-recruitment of HOIP and BCL10	[71]
Myeloid leukemia	HOIP	Knockdown of HOIP increases apoptosis in myeloid leukemia cells	[109]
Breast cancer	Epsin1/2	Heightened epsin levels promote NEMO linear ubiquitination, resulting in sustained NF-κB signaling	[110]
Breast cancer	HOIP	HOIP facilitates p53 polyubiquitination and degradation by stabilizing MDM2	[111]
Breast cancer	SHARPIN	SHARPIN prolongs MDM2 protein stability to facilitate p53 degradation	[112]
Breast cancer	SHARPIN	SHARPIN mediates monoubiquitination of ERα, blocking ERα polyubiquitination and protein degradation	[113]
Breast cancer	HOIL-1	HOIL-1 promots the transcription of ERα and cyclin B1	[114]
Breast cancer	HOIL-1	HOIL-1 promotes YAP polyubiquitination and degradation	[115]
Prostate cancer	PTEN	R173H and R173C mutations of PETN enhance the linear ubiquitination of PTEN, inhibiting PTEN phosphatase activity	[77]
Ovarian cancer	HOIL-1	HOIL-1 promotes PTEN polyubiquitination and degradation	[116]
Renal cell carcinoma	HOIL-1	HOIL-1 facilitates p53 proteolytic ubiquitination	[117]
Renal cell carcinoma	SHARPIN	SHARPIN promotes the ubiquitination and proteasomal degradation of the tumor suppressor Von Hippel-Lindau	[118]
Skin cancer	SHARPIN	SHARPIN promotes Rap1 expression	[119]
Skin cancer	SHARPIN	SHARPIN enhances PRMT5 methyltransferase activity	[120]
Liver cancer	HOIL-1	HOIL-1 mediates the PPARγ/PGC1α complex ubiquitination and protein degradation	[121]
Liver cancer	OTULIN	OTULIN inhibits FADD and RIPK1 kinase-mediated hepatocyte apoptosis	[122]
Lung cancer	SHARPIN	SHARPIN interacts with PRMT5 to regulate histone H3R2 methylation-coupled transcriptional activation	[123]
Lung cancer	HOIL-1	HOIL-1 targets PKCζ for proteasomal degradation to promote tumor survival	[124]
Glioblastoma	OTULIN	OTULIN removes linear ubiquitin conjugated on STAT3, leading to persistent STAT3 signaling	[79]
Gastric cancer	SHARPIN	SHARPIN prevents β-catenin ubiquitination and proteasomal degradation	[125]

Back to article page

ISSN: 1478-811X

Contact us

General enquiries: journalsubmissions@springernature.com