Journal ArticleDOI
Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis.
Marcel Verheij,Marcel Verheij,Ron Bose,Xin Hua Lin,Bei Yao,W. David Jarvis,Steven Grant,Michael J. Birrer,Eva Szabo,Leonard I. Zon,John M. Kyriakis,Adriana Haimovitz-Friedman,Zvi Fuks,Richard Kolesnick +13 more
TLDR
It is reported that ceramide initiates apoptosis through the SAPK cascade and evidence is provided for a signalling mechanism that integrates cytokine- and stress-activated apoptosis.Abstract:
The induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide, is thought to mediate apoptosis in response to tumour-necrosis factor (TNF)-alpha, to Fas ligand and to X-rays. It is not known whether it plays a role in the stimulation of other forms of stress-induced apoptosis. Given that environmental stresses also stimulate a stress-activated protein kinase (SAPK/JNK), the sphingomyelin and SAPK/JNK signalling systems may be coordinated in induction of apoptosis. Here we report that ceramide initiates apoptosis through the SAPK cascade and provide evidence for a signalling mechanism that integrates cytokine- and stress-activated apoptosis.read more
Citations
More filters
Journal ArticleDOI
AP-1 function and regulation.
TL;DR: This work has shown that regulation by heterodimerization between Jun, Fos and ATF proteins, AP-1 activity is regulated through interactions with specific protein kinases and a variety of transcriptional coactivators, and there has been considerable progress in understanding some of the mechanisms and signaling pathways involved in the regulation of AP.
Journal ArticleDOI
AP-1 as a regulator of cell life and death
Eitan Shaulian,Michael Karin +1 more
TL;DR: Interestingly, the growth-promoting activity of c-Jun is mediated by repression of tumour suppressors, as well as upregulation of positive cell cycle regulators, whereas JunB has the converse effect.
Journal ArticleDOI
NF-κB at the crossroads of life and death
Michael Karin,Anning Lin +1 more
TL;DR: The choice between life and death is one of the major events in regulation of the immune system and a major regulator of such life or death decisions is the transcription factor NF-κB as mentioned in this paper.
Journal ArticleDOI
Cellular functions regulated by src family kinases
Sheila M. Thomas,Joan S. Brugge +1 more
TL;DR: This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms leading to their activation, the targets that interact with these kinases, and the biological events that they regulate.
Journal ArticleDOI
Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.
Masao Saitoh,Hideki Nishitoh,Makiko Fujii,Kohsuke Takeda,Kei Tobiume,Yasuhiro Sawada,Masahiro Kawabata,Kohei Miyazono,Hidenori Ichijo +8 more
TL;DR: Evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine‐ and stress‐induced apoptosis.
References
More filters
Journal ArticleDOI
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
TL;DR: The extent of tissue-PCD revealed by this method is considerably greater than apoptosis detected by nuclear morphology, and thus opens the way for a variety of studies.
Journal ArticleDOI
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
TL;DR: The effects of dominant-interfering or constitutively activated forms of various components of the JNK-p38 and ERK signaling pathways demonstrated that activation of JNK and p38 and concurrent inhibition of ERK are critical for induction of apoptosis in these cells.
Journal ArticleDOI
JNK1: A protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain
Benoit Dérijard,Benoit Dérijard,Masahiko Hibi,I-Huan Wu,I-Huan Wu,Tamera Barrett,Bing Su,Tiliang Deng,Michael Karin,Roger J. Davis,Roger J. Davis +10 more
TL;DR: JNK1 is a component of a novel signal transduction pathway that is activated by oncoproteins and UV irradiation and its properties indicate that JNK1 activation may play an important role in tumor promotion.
Journal ArticleDOI
The stress-activated protein kinase subfamily of c-Jun kinases.
John M. Kyriakis,Papia Banerjee,Eleni Nikolakaki,Eleni Nikolakaki,Tianang Dai,Elizabeth A. Rubie,M. F. Ahmad,Joseph Avruch,James R. Woodgett +8 more
TL;DR: The kinase p54s are the principal c-Jun N-terminal kinases activated by cellular stress and tumour necrosis factor (TNF)-α, hence they are designated stress-activated protein kinases, or SAPKs.
Journal ArticleDOI
The Regulation of AP-1 Activity by Mitogen-activated Protein Kinases
TL;DR: The specific roles of three MAPKs, namely ERK, JNK and FRK, in modulation of both the level and activity of AP-1, are discussed.