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Table 1 Substrates of HUWE1-mediated ubiquitination

From: Ubiquitination by HUWE1 in tumorigenesis and beyond

Targets Ubiquitination Type and Linkage Ubiquitination Effects Functional Alteration by ubiquitination References
c-Myc K63-linked poly-ubiquitination c-Myc transactivation Increased cell proliferation [43]
N-Myc K48-linked poly-ubiquitination Degradation Dysregulated neural differentiation; Perturbed HSC self-renewal [60,61,62]
Dvl K63-linked poly-ubiquitination Inhibit Dvl multimerization Negative feedback loop to Wnt signaling [63]
Atoh1 Poly-ubiquitination Phosphorylation-dependent degradation Increased neuronal differentiation [71]
Mcl-1 Poly-ubiquitination Degradation Increased DNA-damage induced apoptosis; Increased hepatocyte apoptosis [77]
p53 Poly-ubiquitination Degradation Reduced cell growth arrest; Increased anti-apoptosis [87]
HDAC2 Poly-ubiquitination Degradation Apoptosis [92]
Miz1; c-Myc/Miz1 K48-linked poly-ubiquitination Degradation JNK activation and apoptosis; Ras signaling suppression; [30, 102]
Cdc6 Poly-ubiquitination Degradation Released from chromatin; Inhibition of preRC assembly [103]
BRCA1 Poly-ubiquitination Degradation Reduced DNA repair [116, 117]
Pol β Mono-ubiquitination Degradation Decreased DNA repair [39]
Pol λ Mono-ubiquitination Degradation Decreased DNA repair; Reduced chromatin binding [40]
HAUSP K63-linked poly-ubiquitination Enhanced HAUSP deubiquitase activity; enhanced transactivation EMT, chromatin modification [124]
TIAM1 Poly-ubiquitination Degradation Enhanced migration, invasion [126]
MyoD Poly-ubiquitination Degradation Myogenesis [138]
H1.3 Poly-ubiquitination Degradation Ovarian epithelial cell transformation; Tumor growth [139]
H2AX Poly-ubiquitination Degradation Decreased DNA repair [142]