The HECT family of E3 ubiquitin ligases: multiple players in cancer development.
The involvement of the homologous to E6-AP carboxyl terminus (HECT)-type E3s in crucial signaling pathways implicated in tumorigenesis is presently an area of intense research and extensive scientific interest. This review highlights recent discoveries on the ubiquitin-mediated degradation of crucial tumor suppressor molecules catalyzed by the HECT-type E3s. By providing a portrait of their protein targets, we intend to link the substrate specificity of HECT-type E3s with their contribution to tumorigenesis. Moreover, we discuss the relevance of targeting the HECT E3s, through the development of small-molecule inhibitors, as an anticancer therapeutic strategy.
Bernassola
Francesca
F
Department of Experimental Medicine and Biochemical Sciences, Biochemistry IDI-IRCCS Laboratory, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy.
Karin
Michael
M
Ciechanover
Aaron
A
Melino
Gerry
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000075702:Nedd4 Ubiquitin Protein Ligases; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013379:Substrate Specificity; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D056827:Endosomal Sorting Complexes Required for Transport; D004791:Enzyme Inhibitors; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; C502830:HUWE1 protein, human; C432966:ITCH protein, human; D000075702:Nedd4 Ubiquitin Protein Ligases; C471639:UBE3A protein, human; C471642:WWP1 protein, human; D044767:Ubiquitin-Protein Ligases