Itch: a HECT-type E3 ligase regulating immunity, skin and cancer.
The HECT-type E3 ubiquitin ligase (E3) Itch is absent in the non-agouti-lethal 18H or Itchy mice, which develop a severe immunological disease, including lung and stomach inflammation and hyperplasia of lymphoid and hematopoietic cells. The involvement of Itch in multiple signaling pathways and pathological conditions is presently an area of extensive scientific interest. This review aims to bring together a growing body of work exploring Itch-regulated biological processes, and to highlight recent discoveries on the regulatory mechanisms modulating its catalytic activity and substrate recognition capability. Our contribution is also an endeavor to correlate Itch substrate specificity with the pathological defects manifested by the mutant Itchy mice.
Melino
G
G
IDI-IRCCS Biochemistry Laboratory, Department of Experimental Medicine and Biochemical Sciences, University of Rome 'Tor Vergata', Via Montpellier 1, Rome 00133, Italy.
Gallagher
E
E
Aqeilan
R I
RI
Knight
R
R
Peschiaroli
A
A
Rossi
M
M
Scialpi
F
F
Malatesta
M
M
Zocchi
L
L
Browne
G
G
Ciechanover
A
A
Bernassola
F
F
D000818:Animals; D016923:Cell Death; D066246:ErbB Receptors / Q000378:metabolism; D007107:Immune System / Q000378:metabolism* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009369:Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D010766:Phosphorylation; D021381:Protein Transport; D019707:Receptors, Chemokine / Q000378:metabolism; D012097:Repressor Proteins / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D013379:Substrate Specificity; D050052:TRPC Cation Channels / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D019707:Receptors, Chemokine; D012097:Repressor Proteins; D050052:TRPC Cation Channels; D016212:Transforming Growth Factor beta; D025801:Ubiquitin; C432966:ITCH protein, human; C471637:Itch protein, mouse; D044767:Ubiquitin-Protein Ligases; D066246:ErbB Receptors