Table 3.
Multiple experimental studies of necroptosis can be associated with different model-predicted modes of execution
| Refs. | Cell type | Quote(s) from article | Interpretation | Possible execution mode(s) |
|---|---|---|---|---|
| Feoktistova et al. (65) | HCAC (HeLa) | "[T]he deletion of A20 in HeLa or HaCaT cells had no effect on the TNF-mediated cell death sensitivity" | A20 ⇓ TTD ⇔ | M3, M4 |
| Hitomi et al. (9) | HTL (Jurkat) | "[I]nhibition of CYLD expression in Jurkat cells also attenuated necroptosis" | CYLD ⇓ TTD ⇑ | M2, M4 |
| Liu et al. (66) | HCN (HT-22) | "RIP1 and its deubiquitinase CYLD are required for TNF-induced necrosis of HT-22 cells" | CYLD ⇓ TTD ⇑ | M2, M4 |
| Moquin et al. (11) | MEF | "CYLD regulates RIP1 ubiquitination in the TNF-α-induced necrosome, but not in the TNFR-1 signaling complex"" Although CYLD was recruited to TNFR-1 in a ligand-dependent manner, RIP1 ubiquitination was not affected in CYLD−/− MEFs" |
CYLD ⇓ TTD ⇑ | M4 (see text) |
| Vanlangenakker et al. (25) | MFS (L929) | "[W]e and others previously showed that CYLD repression protects L929 cells from TNF-induced necroptosis"" [W]e were surprised to find that A20 depletion had an opposite effect and greatly sensitized the cells to death"" [W]e found that TRADD depletion in L929 cells did not affect TNF-induced necroptosis" |
CYLD ⇓ TTD ⇑ A20 ⇓ TTD ⇓ TRADD ⇓ TTD ⇔ |
M2 |
| Wertz et al. (13) | HEK (HEK293T) | "Co-transfection of wild-type A20 deubiquitinates RIP in HEK293T cells" | A20 ⇓ TTD ⇑ | M1 |
| Wertz et al. (13) | MEF | "However, in the absence of A20, RIP1 will neither be deubiquitinated nor targeted for proteasomal degradation. Indeed, RIP recruited to activated TNFR1 remained hyperubiquitinated and was stabilized in A20−/− MEFs" | A20 ⇓ TTD ⇑ | M1 |
| Wright et al. (20) | HCAC (HeLa) | "RIP1 ubiquitination [was] inhibited by wild-type (Wt) CYLD but not a catalytically inactive CYLD mutant (Mut)" | CYLD ⇓ TTD ⇑ | M2, M4 |
In the second column, the specific cell line used (if applicable) is included in parentheses. HCAC, human cervical adenocarcinoma; HCN, hippocampal neuron; HEK, human embryonic kidney; HTL, human T lymphocyte; MEF, mouse embryonic fibroblast; MFS, mouse fibrosarcoma. ⇓, decrease; ⇑, increase; ⇔, no change.