1. Academic Validation
  2. TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3

TRADD mediates the tumor necrosis factor-induced apoptosis of L929 cells in the absence of RIP3

  • Sci Rep. 2017 Nov 23;7(1):16111. doi: 10.1038/s41598-017-16390-6.
Xixi Chang 1 Lili Wang 1 Zicheng Wang 1 Shuai Wu 1 Xiaoming Zhu 1 Shiping Hu 1 Yu Wang 2 Jiyun Yu 3 Guozhu Chen 4
Affiliations

Affiliations

  • 1 Department of Frontier for Biological Treatment, Beijing Institute of Basic Medical Science, Beijing, 100850, China.
  • 2 Department of Frontier for Biological Treatment, Beijing Institute of Basic Medical Science, Beijing, 100850, China. [email protected].
  • 3 Department of Frontier for Biological Treatment, Beijing Institute of Basic Medical Science, Beijing, 100850, China. [email protected].
  • 4 Department of Frontier for Biological Treatment, Beijing Institute of Basic Medical Science, Beijing, 100850, China. [email protected].
Abstract

Receptor-interacting protein kinase 3 (RIP3) is a critical initiator in mediating Necroptosis induced by tumor necrosis factor alpha (TNFα) in L929 cells, so knockdown of RIP3 inhibits TNFα-induced L929 cell Necroptosis. However, RIP3 knockdown was shown to switch TNFα-induced Necroptosis to Apoptosis in L929 cells in other studies. Therefore, whether RIP3 knockdown blocks the TNFα-induced death of L929 cells is controversial. In this study, TNFα activated Caspase pathway and induced cell death in RIP3 knockdown L929 cells, and the RIP3-independent cell death had been blocked by Z-VAD-FMK (pan-caspase inhibitor) or Caspase 8 knockdown, demonstrating that RIP3 knockdown switched TNFα-induced Necroptosis to caspase-dependent Apoptosis. Although both TNF Receptor type 1-associated death domain protein (TRADD) and RIP1 have been reported to mediate TNFα-induced Apoptosis, the knockdown of TRADD, but not RIP1, suppressed TNFα-induced activation of the Caspase pathway and subsequent Apoptosis in RIP3 knockdown L929 cells. In addition, TRADD bound and activated Caspase 8 during the RIP3-independent Apoptosis process, indicating that TRADD initiates RIP3-independent Apoptosis by activating the Caspase pathway. Collectively, we identified the target and mechanism underlying RIP3-independent Apoptosis and elucidated the coordinated roles of RIP3 and TRADD in mediating the programmed cell death of L929 cells following TNFα stimulation.

Figures
Products