Changes in FADD levels, distribution, and phosphorylation in TNFα-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent

Xiaoying Zhang, Raghuveer Vallabhaneni, Patricia A. Loughran, Richard Shapiro, Xiao-Ming Yin, Youzhong Yuan, Timothy R. Billiar

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

FADD/MORT1 (The adaptor protein of Fas Associate Death Domain/Mediator of Receptor Induced Toxicity) is essential for signal transduction of death receptor signaling. We have previously shown that FADD is significantly up-regulated in TNFα/ActD induced apoptosis. Over-expression of FADD also induces death of lung cancer cells and primary hepatocytes. We hypothesize that the increase in detectable FADD levels require the proximal steps in apoptotic signaling and speculated that FADD would be redistributed in cells destined to undergo apoptosis. We show that monomeric non-phosphorylated FADD is up-regulated in hepatocytes treated with TNFα/ActD and that it accumulates in the cytoplasm. Nuclear phosphorylated FADD decreases with TNFα/ActD treatment. Dimeric FADD in the cytoplasm remains constant with TNFα/ActD. The change in FADD levels and distribution was dependent on caspase-3, caspase-8 activity and the presence of BID. Thus, changes in FADD levels and distribution are downstream of caspase activation and mitochondria changes that are initiated by the formation of the DISC complex. Changes in FADD levels and distribution may represent a novel feed-forward mechanism to propagate apoptosis signaling in hepatocytes.

Original languageEnglish (US)
Pages (from-to)983-992
Number of pages10
JournalApoptosis
Volume13
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

Phosphorylation
Caspase 8
Caspase 3
Hepatocytes
Death Domain Receptors
Apoptosis
Cytoplasm
Signal transduction
Mitochondria
Caspases
Toxicity
Signal Transduction
Lung Neoplasms
Chemical activation
Cells
Proteins

Keywords

  • Apoptosis
  • BID
  • Caspase-8
  • Caspse-3
  • Dimerization
  • FADD
  • Hepatocytes
  • Nuclear/cytoplasm translocation
  • Phosphorylation
  • TNFα

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Changes in FADD levels, distribution, and phosphorylation in TNFα-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent. / Zhang, Xiaoying; Vallabhaneni, Raghuveer; Loughran, Patricia A.; Shapiro, Richard; Yin, Xiao-Ming; Yuan, Youzhong; Billiar, Timothy R.

In: Apoptosis, Vol. 13, No. 8, 08.2008, p. 983-992.

Research output: Contribution to journalArticle

Zhang, Xiaoying ; Vallabhaneni, Raghuveer ; Loughran, Patricia A. ; Shapiro, Richard ; Yin, Xiao-Ming ; Yuan, Youzhong ; Billiar, Timothy R. / Changes in FADD levels, distribution, and phosphorylation in TNFα-induced apoptosis in hepatocytes is caspase-3, caspase-8 and BID dependent. In: Apoptosis. 2008 ; Vol. 13, No. 8. pp. 983-992.
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