Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis.
FIP-3 (14.7K interacting protein) was discovered during a search for cell proteins that could interact with an adenovirus protein (Ad E3-14.7K) that had been shown to prevent tumor necrosis factor (TNF)-alpha-induced cytolysis. FIP-3, which contains leucine zippers and a zinc finger domain, inhibits both basal and induced transcriptional activity of NF-kappaB and causes a late-appearing apoptosis with unique morphologic manifestations. Ad E3-14.7K can partially reverse apoptotic death induced by FIP-3. FIP-3 also was shown to bind to other cell proteins, RIP and NIK, which previously had been described as essential components of TNF-alpha-induced NF-kappaB activation. In addition, FIP-3 inhibited activation of NF-kappaB induced by TNF-alpha, the TNFR-1 receptor, RIP, NIK, and IKKbeta, as well as basal levels of endogenous NF-kappaB in 293 cells. Because the activation of NF-kappaB has been shown to inhibit apoptosis, FIP-3 appears both to activate a cell-death pathway and to inhibit an NF-kappaB-dependent survival mechanism.
Pubmed ID: 9927690
- Li Y
- Kang J
- Friedman J
- Tarassishin L
- Ye J
- Kovalenko A
- Wallach D
- Horwitz MS
Proceedings of the National Academy of Sciences of the United States of America
February 2, 1999
- Agency: NCI NIH HHS, Id: 5T32CA 09060
- Agency: NCI NIH HHS, Id: CA13330
- Agency: NCI NIH HHS, Id: R01 CA72963
- Adenovirus E3 Proteins
- Amino Acid Sequence
- Carrier Proteins
- Cell Line
- Cell Survival
- Glutathione Transferase
- I-kappa B Kinase
- Leucine Zippers
- Molecular Sequence Data
- Molecular Weight
- NF-kappa B
- Protein Kinases
- Protein-Serine-Threonine Kinases
- Receptor-Interacting Protein Serine-Threonine Kinases
- Recombinant Fusion Proteins
- Recombinant Proteins
- Sequence Alignment
- Sequence Homology, Amino Acid
- Transcriptional Activation
- Tumor Necrosis Factor-alpha
- Zinc Fingers
- Atypical mycobacteriosis, familial is related to genes IKBKG, NEMO, FIP3, IP2, IPD2, AMCBX1.
- Invasive pneumococcal disease, recurrent isolated, 2 is related to genes IKBKG, NEMO, FIP3, IP2, IPD2, AMCBX1.
- Ectodermal dysplasia, hypohidrotic, with immune deficiency is related to genes IKBKG, NEMO, FIP3, IP2, IPD2, AMCBX1.
- Ectodermal, dysplasia, anhidrotic, lymphedema and immunodeficiency is related to genes IKBKG, NEMO, FIP3, IP2, IPD2, AMCBX1.
- Immunodeficiency, isolated is related to genes IKBKG, NEMO, FIP3, IP2, IPD2, AMCBX1.
- Incontinentia pigmenti, type II is related to genes IKBKG, NEMO, FIP3, IP2, IPD2, AMCBX1 which are x-linked dominant according to the OMIM database.