Table 1 Substrates of HUWE1-mediated ubiquitination
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 | |
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; | |
Cdc6 | Poly-ubiquitination | Degradation | Released from chromatin; Inhibition of preRC assembly | [103] |
BRCA1 | Poly-ubiquitination | Degradation | Reduced DNA repair | |
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] |