Table 3.
Main molecules involved in necroptosis.
| Molecules | Biological Function | Type of Programmed Cell Death |
References |
|---|---|---|---|
| IFN-γ | Responsible for triggering necroptosis. | Necroptosis | [136,140,141,142] |
| LPS | Responsible for triggering necroptosis. | Necroptosis | [136,140,141,142,151] |
| RIPK1 | A key regulator of the assembly of complex IIb (RIPK1-RIPK3-MLKL) during necroptosis. | Necroptosis | [127,131,137,138,139,140,141,142,143,145,146,147,148,149,150,151,152,155] |
| RIPK3 | Serine/threonine-protein kinase that activates necroptosis. | Necroptosis | [127,131,137,138,139,140,141,142,146,147,149,152,155] |
| MLKL | Pseudokinase that plays a key role in TNF-induced necroptosis. | Necroptosis | [127,131,137,138,139,140,141,142,146,147,155] |
| TNFR1 | Its activation allows the recruitment of TRADD, RIP1, and TRAF2. | Necroptosis | [140,141,142,145,146,147] |
| TRADD | It is identified as a target protein for TNF-induced necroptosis in the absence of RIPK1. | Necroptosis | [140,141,142,145,146,147] |
| FADD | It recruits the initiator caspase-8, forming the death-inducing signaling complex (DISC). | Necroptosis | [148] |
| TRAF2 | Through TNF-induced NF-κB activation, it is able to protect cells, inhibiting necroptotic cell death. | Necroptosis | [140,141,142] |
| TRAF5 | Through TNF-induced NF-κB activation, it is able to protect cells, inhibiting necroptotic cell death. | Necroptosis | [140,141,142] |
| LUBAC | It regulates necrosome-associated RIPK1 ubiquitination. | Necroptosis | [140,141,142,143] |
| cIAP1 | It ubiquitinates NF-kB, inducing kinase (NIK) to suppress non-canonical NF-kB signaling and RIPK1 to promote cell survival. | Necroptosis | [140,141,142,143,148] |
| cIAP2 | It ubiquitinates NF-kB, inducing kinase (NIK) to suppress non-canonical NF-kB signaling and RIPK1 to promote cell survival. | Necroptosis | [140,141,142,143,148] |
| IKKα | Together with IKKβ, it constitutes IkB kinase complex. | Necroptosis | [143,144,148] |
| IKKβ | Together with IKKα, it constitutes IkB kinase complex. | Necroptosis | [143,144,148] |
| NEMO | Together with IKKα and IKKβ, it constitutes IkB kinase complex. | Necroptosis | [143,144] |
| TAK1 | Serine/threonine kinase, which phosphorylates RIPK1, regulating its interaction with RIPK3 and promoting necroptosis. It constitutes TAK1 complex. | Necroptosis | [127,143,144,148] |
| TAB1 | Together with TAK1 and TAB2, it constitutes TAK1 complex. | Necroptosis | [143,144] |
| TAB2 | Together with TAK1 and TAB1, it constitutes TAK1 complex. | Necroptosis | [143,144] |
| NF-kB | Its activation, through TAK1 and IKK complexes, allows the cell survival. | Necroptosis | [144] |
| CYLD | Deubiquitinase, which induces TNF-alpha-induced necroptosis. | Necroptosis | [145,146,147] |
| E3-ligase PELI1 | Negatively regulates necroptosis by reducing RIPK3 expression. | Necroptosis | [149] |