Ro52/SSA sensitizes cells to death receptor-induced apoptosis by down-regulating c-FLIP(L)

Cell Biol Int. 2012 May 1;36(5):463-8. doi: 10.1042/CBI20110322.

Abstract

Ro52/SSA is an autoantigen that presents in patients with SS (Sjögren's syndrome) and SLE (systemic lupus erythematosus). It increases cell death and redistributes itself to apoptotic blebs, but its pro-apoptotic function has not been completely identified. Overexpression of Ro52/SSA promoted cell apoptosis induced by DR (death receptor) in caspase-8-dependent manner. Ro52/SSA expression down-regulated c-FLIP(L) [cellular (Fas-associated death domain)-like interleukin 1β-converting enzyme-inhibitory protein long form] expression, and Ro52/SSA siRNAs (small interfering RNAs) increased c-FLIP(L) production, indicating that Ro52/SSA plays a role in c-FLIP(L) regulation. Ro52/SSA negatively regulated c-FLIP(L) transcriptional level probably by suppressing NF-κB (nuclear factor κB) signalling. The data suggest that Ro52/SSA is involved in DR-mediated apoptosis by regulating c-FLIP(L).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis*
  • CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism*
  • Caspase 8 / metabolism
  • Cell Line, Tumor
  • Down-Regulation
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • NF-kappa B / metabolism
  • RNA Interference
  • RNA, Small Interfering
  • Receptors, Death Domain / metabolism*
  • Ribonucleoproteins / biosynthesis
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Signal Transduction

Substances

  • Apoptosis Regulatory Proteins
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • RNA, Small Interfering
  • Receptors, Death Domain
  • Ribonucleoproteins
  • SS-A antigen
  • Caspase 8