Sp1 Phosphorylation Regulates Apoptosis via Extracellular FasL-Fas Engagement
Open Access
- 1 February 2001
- journal article
- Published by Elsevier BV in Journal of Biological Chemistry
- Vol. 276 (7), 4964-4971
- https://doi.org/10.1074/jbc.m009251200
Abstract
Apoptosis of smooth muscle cells (SMC) in atherosclerotic vessels can destabilize the atheromatus plaque and result in rupture, thrombosis, and sudden death. In efforts to understand the molecular processes regulating apoptosis in this cell type, we have defined a novel mechanism involving the ubiquitously expressed transcription factor Sp1. Subtypes of SMC expressing abundant levels of Sp1 produce the death agonist, Fas ligand (FasL) and undergo greater spontaneous apoptosis. Sp1 activates the FasL promoter via a distinct nucleotide recognition element whose integrity is crucial for inducible expression. Inducible FasL promoter activation is also inhibited by a dominant-negative form of Sp1. Increased SMC apoptosis is preceded by Sp1 phosphorylation, increased FasL transcription, and the autocrine/paracrine engagement of FasL with its cell-surface receptor, Fas. Inducible FasL transcription and apoptosis are blocked by dominant-negative protein kinase C-ζ, whose wild-type counterpart phosphorylates Sp1. Thus, Sp1 phosphorylation is a proapoptotic transcriptional event in vascular SMC and, given the wide distribution of this housekeeping transcription factor, may be a common regulatory theme in apoptotic signal transduction.Keywords
This publication has 50 references indexed in Scilit:
- FasL promoter activation by IL-2 through SP1 and NFAT but not Egr-2 and Egr-3European Journal of Immunology, 1999
- Apoptosis in the Atherosclerotic PlaqueArteriosclerosis, Thrombosis, and Vascular Biology, 1998
- Transcriptional Regulation of the Human FasL Promoter-Enhancer RegionPublished by Elsevier BV ,1998
- Signal transduction through atypical PKCs, but not the EGF receptor, is necessary for UVC-induced AP-1 activation in immortal murine cellsOncogene, 1997
- Molecular and cell biology of native coronary and vein-graft atherosclerosisCoronary Artery Disease, 1997
- Selenite suppression of cadmium-induced testicular apoptosisToxicology, 1997
- Activation of Protein Kinase C (α, β, and ζ) by Insulin in 3T3/L1 CellsPublished by Elsevier BV ,1997
- Characterization of a Renal Epithelial Cell Model of Apoptosis Using Okadaic Acid and the NRK-52E Cell LineToxicologic Pathology, 1994
- Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content.Heart, 1993
- GC box binding induces phosphorylation of Sp1 by a DNA-dependent protein kinaseCell, 1990