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Proteomic analysis of TRAIL-induced endogenous RIPK3-dependent necrosome complex

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known inducer of apoptosis via formation of the primary death-inducing signaling complex (TRAIL-DISC) at the level of membrane death receptors (DR4 and DR5) which recruit successively FADD and caspase-8. TRAIL can also induce necroptosis when caspases are inhibited. Necroptosis is a regulated cell death dependent on the formation of a cytosolic necrosome complex which includes RIPK1, RIPK3 and MLKL proteins. Elucidating the molecular mechanisms involved in TRAIL-induced necroptosis might provide new insights into the TRAIL death signaling pathway. Here, we report the analysis by mass spectrometry of endogenous RIPK3-dependent necrosome complex constituents upon necroptosis induced by TRAIL/z-VAD/Birinapant (TzB) in HT29 cells. Besides characterization of RIPK1, RIPK3, MLKL, FADD, caspase-8, we find TRIM21 as a new constituent of the necrosome complex. Moreover RIPK1, RIPK3, MLKL, P-MLKL, FADD, caspase-8 and TRIM21 are also found associated to the native TRAIL-DISC upon TzB stimulation showing initiation of the necrotic pathway at the level of TRAIL death receptors in HT29 cells. Finally, TRIM21 may positively modulate necroptosis induction by downregulating NF-kB activation.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human) Colon

TISSUE(S): Ht-29 Cell

SUBMITTER: Melanie Lagarrigue

LAB HEAD: Charles Pineau

PROVIDER: PXD003383 | Pride | 2021-03-18

REPOSITORIES: Pride

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			Action	DRS
	243_IPRIPK3_0h_Exp1.RAW	Raw
	243_IPRIPK3_0h_Exp1.dat	Other
	243_IPRIPK3_0h_Exp1.pride.mgf.gz	Mgf
	243_IPRIPK3_0h_Exp1.pride.mztab.gz	Mztab
	243_IPRIPK3_0h_Exp1.xml.gz	Xml

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