A20 takes on tumors: tumor suppression by an ubiquitin-editing enzyme

Differential genomic targeting of the transcription factor TAL1 in alternate haematopoietic lineages

“…Interestingly, TAL1 may also decrease apoptosis via upregulation of Cd226, which is involved in the resistance of thymocytes to apoptosis (Fang et al, 2009). Finally, we identified three tumour suppressor genes: Tnfaip3 (Malynn and Ma, 2009), Pten (Li et al, 1997;Gutierrez et al, 2009) and Lrp12/st7 (Zenklusen et al, 2001)) that are repressed by TAL1. Finally, we observed a significant enrichment (2.8-fold; P-value ¼ 5.488e-13, proportions test with continuity correction) of TAL1 peaks near the signature genes associated with TAL1 expression in T-ALL patients (Ferrando et al, 2002), suggesting that many of these signature genes are direct targets of TAL1.…”

A20 and ABIN-3 possibly promote regression of trehalose 6,6′-dimycolate (TDM)-induced granuloma by interacting with an NF-kappa B signaling protein, TAK-1

“…Previous studies suggested a crucial role of A20 in the pathogenesis of certain diseases in which NF-kappa is deeply involved. For instance, A20-mediated NF-kappa B suppression is involved in the suppression of tumors [38] and cardiac fibrosis [39]. In addition, a mutation of A20 causes various autoimmune diseases and chronic inflammatory diseases [40].…”

Functional Properties of CYLD

“…More recently, A20 was discovered to interact with the E3 ligase RNF11 and the E2 enzymes UBC13 Ubc5c, the latter of which antagonizes the activity of the E3 ligases TRAF6, TRAF2 and clAP1, thereby providing a direct mechanism of action of A20 terminating NF-κB activation [26,27]. Taken together, A20 represents an OTU with a central role in regulating inflammation, and mutations are associated with many autoimmune pathologies as well as B-cell malignancies, such as Hodgkin lymphomas [28].…”