Table 1.
List of E3 ligases and DUBs that modulate T cell development.
| Ubiquitinase | Substrate | Cko/ko mice | Phenotype | Ref. |
|---|---|---|---|---|
| E3 ligases | ||||
| Itch | Notch | Itch-/-; Lck-Notch1 tg+ | -reduces DP and increases DN thymocytes -reduces apoptosis in the thymus and increases phospho-AKT signaling |
(14) |
| Mib1 | Dll1, Dll4 | Mib1-/- | -impairs Dll1 and Dll4 endocytosis -reduces DP and increases DN thymocytes |
(15) |
| Fbxw7 | c-Myc | Lck-Cre; Fbxw7fl/fl | -promotes cell cycle exit -leads to hyperproliferation in thymocytes -increases DP thymocytes -enforces GATA3 expression |
(16) |
| Fbxl1 | Cdkn1b | Fbxl1-/- | -resultes in an incomplete DN3-DN4 developmental block | (17) |
| Fbxl12 | Cdkn1b | Lck-Cre; Fbxl12fl/fl | -blocks DN3-DN4 transition | (17) |
| TRIM21 | SOCS3 | TRIM21-/- | -increases number of thymocytes -reduces frequency of DN cells | (18) |
| GRAIL | TCR-CD3 | GRAIL-/- | -upregulates the function of tTregs | (19) |
| VHL | HIF-1α | Lck-Cre; Vhlfl/fl | -increases cell death and caspase activity -reduces TCR-mediated Ca2+ signaling |
(20) |
| TRAF3 | TCPTP | Lck-Cre; TRAF3fl/fl | -increases number of Treg cells in the thymus | (21) |
| TRAF6 | NF-kB essential modifier (NEMO) |
TRAF6-/- | -reduces autoimmunity -reduces Aire expression -reduces Treg cells |
(22) |
| c-Cbl | CD5, TCRζ, Zap-70, SLAP, BIM | c-Cbl-/- | -increases TCR signaling -increases DP thymocytes -increased expression of CD3, CD5, and CD69 -enhances positive Selection of CD4+ T Cells |
(23, 24) |
| Cbl-b | Foxp3, p85 | Cbl-b-/- | -regulates tTregs -reduces mature SP thymocytes |
(25) |
| MARCH1 | MHCII | MARCH1-/- | -reduces tTregs | (26) |
| DUBs | ||||
| USP4 | HUWE1 | USP4-/- | -induces IR-induced apoptosis in thymus | (27) |
| USP7 | Caspase 3 | / | -regulates the apoptosis of thymocytes via interacting with caspase 3 | (28) |
| USP8 | GADS, CHMP5 | CD4-cre;USP8fl/fl | -diminishes thymocyte proliferation | (29–34) |
| USP9X | Themis | USP9X-/- | -reduces thymic cellularity | (35–39) |
| CYLD | LCK | CYLD-/- | -regulates DP-SP transition | (40) |
| MYSM1 | IRF2, IRF8 | MYSM1-/- | -reduces thymus sizes and CD8+ T-cell numbers | (41, 42) |
| A20 | GITR | CD4-cre;A20fl/fl | -increases CD69 expression within NKT thymocytes | (13, 43) |
| BAP1 | H2AK119 | Rosa26CreERT2; Bap1fl/fl | -causes a block at the DN3 stage | (44) |