Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes.

Fas-apoptosis inhibitory molecule (FAIM) is inducibly expressed in B lymphocytes and had been shown to antagonize Fas-mediated killing of B-cell lines in vitro. However, its mechanism and role in vivo are unknown. We have generated faim(-/-) mice and found these mutants to be viable. In contrast to fas(-/-) mice, faim(-/-) mice have normal B- and T-cell populations. However, faim(-/-) B cells and thymocytes show increased sensitivity to Fas-triggered apoptosis in vitro, and faim(-/-) mice suffer greater mortality and exhibit exacerbated liver damage in response to Fas (CD95) engagement in vivo. The lack of FAIM results in greater activation of caspase-8 and -3 in Fas-stimulated thymocytes. Detailed biochemical analyses further reveal the decreased expression of c-FLIP(L) and c-FLIP(R) in faim(-/-) thymocytes and increased association of caspase-8 with Fas in Fas-activated mutant cells. Decreased levels of c-FLIP(L) and c-FLIP(R) are also evident in faim(-/-) liver. Thus, FAIM plays a novel role in modulating Fas-mediated apoptosis and acts through influencing the expression of c-FLIP and regulating the physical binding of caspase-8 to Fas.

Pubmed ID: 19300454


  • Huo J
  • Xu S
  • Guo K
  • Zeng Q
  • Lam KP


Cell death and differentiation

Publication Data

July 16, 2009

Associated Grants


Mesh Terms

  • Animals
  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal
  • Antigens, CD95
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • B-Lymphocytes
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Caspase 3
  • Caspase 8
  • Dexamethasone
  • Fas Ligand Protein
  • Gene Deletion
  • Hepatocytes
  • Immunologic Factors
  • Liver
  • Mice
  • Mice, Knockout
  • T-Lymphocytes
  • Tumor Necrosis Factor-alpha