Journal of Cell Communication and Signaling

, Volume 6, Issue 3, pp 155–168

Apoptotic potential of Fas-associated death domain on regulation of cell death regulatory protein cFLIP and death receptor mediated apoptosis in HEK 293T cells

Research Article

DOI: 10.1007/s12079-012-0166-2

Cite this article as:
Ranjan, K., Surolia, A. & Pathak, C. J. Cell Commun. Signal. (2012) 6: 155. doi:10.1007/s12079-012-0166-2

Abstract

Fas-associated death domain (FADD) is a common adaptor molecule which plays an important role in transduction of death receptor mediated apoptosis. The FADD provides DED motif for binding to both procaspase-8 and cFLIP molecules which executes death receptor mediated apoptosis. Dysregulated expression of FADD and cFLIP may contribute to inhibition of apoptosis and promote cell survival in cancer. Moreover elevated intracellular level of cFLIP competitively excludes the binding of procaspase-8 to the death effector domain (DED) of FADD at the DISC to block the activation of death receptor signaling required for apoptosis. Increasing evidence shows that defects in FADD protein expression are associated with progression of malignancies and resistance to apoptosis. Therefore, improved expression and function of FADD may provide new paradigms for regulation of cell proliferation and survival in cancer. In the present study, we have examined the potential of FADD in induction of apoptosis by overexpression of FADD in HEK 293T cells and validated further its consequences on the expression of pro and anti-apoptotic proteins besides initiation of death receptor mediated signaling. We have found deficient expression of FADD and elevated expression of cFLIPL in HEK 293T cells. Our results demonstrate that over expression of FADD attenuates the expression of anti-apoptotic protein cFLIP and activates the cascade of extrinsic caspases to execution of apoptosis in HEK 293T cells.

Keywords

ApoptosisFas associated death domain (FADD)cFLIPDeath receptor mediated apoptosis

Abbreviations

DED

Death Effector Domain

DISC

Death-Inducing Signaling Complex

cFLIP

Cellular fas-associated death domain-like interleukin-1-β- converting enzyme-inhibitory protein

CHX

Cycloheximide

CD 95L

CD 95 ligand

Copyright information

© The International CCN Society 2012

Authors and Affiliations

  1. 1.Cell Biology Department, School of Biological Sciences & BiotechnologyIndian Institute of Advanced ResearchKobaIndia
  2. 2.Molecular Biophysics UnitIndian Institute of ScienceBangaloreIndia