ITCH as a potential therapeutic target in human cancers.
Semin Cancer Biol
; 67(Pt 2): 117-130, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-32165318
ABSTRACT
The ITCH/AIP4 ubiquitin E3 ligase was discovered independently by two groups searching for atrophin-1 interacting proteins and studying the genetics of mouse coat color alteration, respectively. ITCH is classified as a NEDD4 family E3 ligase featured with the C-terminal HECT domain for E3 ligase function and WW domains for substrate recruiting. ITCH deficiency in the mouse causes severe multi-organ autoimmune disease. Its roles in maintaining a balanced immune response have been extensively characterized over the past two and a half decades. A wealth of reports demonstrate a multifaceted role of ITCH in human cancers. Given the versatility of ITCH in catalyzing both proteolytic and non-proteolytic ubiquitination of its over fifty substrates, ITCH's role in malignancies is believed to be context-dependent. In this review, we summarize the downstream substrates of ITCH, the functions of ITCH in both tumor cells and the immune system, as well as the implications of such functions in human cancers. Moreover, we describe the upstream regulatory mechanisms of ITCH and the efforts have been made to target ITCH using small molecule inhibitors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Ubiquitina-Proteína Ligasas
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Semin Cancer Biol
Asunto de la revista:
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos