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Cited by 23Cell death mechanisms and regulationCancer-related Molecular PathwaysDeath, Funerary Practices, and Mourning

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

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Ranjan, Kishu, Surolia, Avadhesha, Pathak, Chandramani·2012·Journal of Cell Communication and Signaling
DOI 10.1007/s12079-012-0166-2PMC PMC3421020
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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 cFLIP(L) 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.

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  • Apoptotic bodies are selectively ingested by phagocytic cells to avoid local release of cell contents and related local inflammation.

    “The apoptotic bodies are further selectively ingested by phagocytic cells to avoid local release of cell contents and related local inflammation [21,22,23].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [23]

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Metadata

Authors
Ranjan, K., Surolia, A., & Pathak, C.
Affiliations
  • Indian Institute of Advanced Research (IN)
  • Indian Institute of Science Bangalore (IN)
Corresponding author
  • Surolia, Avadhesha
  • Pathak, Chandramani
ORCID
Venue
Journal of Cell Communication and Signaling
Publisher
Wiley
Published
2012-07-12
Volume
6
Issue
3
Pages
155-168
ISSN
  • 1873-9601 (ISSN-L)
  • 1873-961X
DOI
10.1007/s12079-012-0166-2
PMC
PMC3421020
OpenAlex
W2068704946
Cited by
23
References
1
Citations by year
2025: 1 · 2024: 3 · 2023: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 3
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Journal of Cell Communication and Signaling (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
University of Colorado Denver
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Social Sciences › Anthropology › Death, Funerary Practices, and Mourning
Keywords
FADD, c-FLIP, death receptor-mediated apoptosis, caspase-8, death effector domain, death-inducing signaling complex, anti-apoptotic proteins, apoptosis resistance, HEK293T cells

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