Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling.

Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. Research Abstract Details 

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Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. Abstract Text:

S Chen,D C Guttridge,E Tang,S Shi,K Guan,C Y Wang,

The activation of nuclear factor kappaB (NF-kappa B) plays a pivotal role in the regulation of tumor necrosis factor (TNF)-mediated apoptosis. However, little is known about the regulation of TNF-mediated apoptosis by other signaling pathways or growth factors. Here, unexpectedly, we found that bone morphogenetic protein (BMP)-2 and BMP-4 inhibited TNF-mediated apoptosis by inhibition of caspase-8 activation in C2C12 cells, a pluripotent mesenchymal cell line that has the potential to differentiate into osteoblasts depending on BMP stimulation. Utilizing both a trans-dominant IkappaBalpha inhibitor of NF-kappaB expressed in C2C12 cells and IkappaB kinase beta-deficient embryonic mouse fibroblast, we show that BMP-mediated survival was independent of NF-kappaB activation. Rather, the antiapoptotic activity of BMPs functioned through the Smad signaling pathway. Thus, these findings provide the first report of a BMP/Smad signaling pathway that can inhibit TNF-mediated apoptosis, independent of the prosurvival activity of NF-kappaB. Our results suggest that BMPs not only stimulate osteoblast differentiation but can also promote cell survival during the induction of bone formation, offering new insight into the biological functions of BMPs.

Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. Publishing Authors By Initials

S Chen,DC Guttridge,E Tang,S Shi,K Guan,CY Wang,

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

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Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: The Journal of biological chemistry

VOLUME: 276

Page Numbers: 39259-63

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 10

MONTH: 08

YEAR: 2001

Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. Information

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LANGUAGE: eng

NlmUniqueID: 2985121

Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: metabolism

Chemical & Substance for Abstract: Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling. Information

Substance Name: Caspases

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Suppression of tumor necrosis factor-mediated apoptosis by nuclear factor kappaB-independent bone morphogenetic protein/Smad signaling.

AFFILIATION: Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109, USA.

Country: United States

AGENCY: United States NIDCR

GRANT: DE13848

ACRONYM: DE

MEDLINETA: J Biol Chem

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