AP-1 in cell proliferation and survival.
Eitan Shaulian,Michael Karin +1 more
TLDR
Amongst the Jun proteins, c-Jun is unique in its ability to positively regulate cell proliferation through the repression of tumor suppressor gene expression and function, and induction of cyclin D1 transcription.Abstract:
A plethora of physiological and pathological stimuli induce and activate a group of DNA binding proteins that form AP-1 dimers. These proteins include the Jun, Fos and ATF subgroups of transcription factors. Recent studies using cells and mice deficient in individual AP-1 proteins have begun to shed light on their physiological functions in the control of cell proliferation, neoplastic transformation and apoptosis. Above all such studies have identified some of the target genes that mediate the effects of AP-1 proteins on cell proliferation and death. There is evidence that AP-1 proteins, mostly those that belong to the Jun group, control cell life and death through their ability to regulate the expression and function of cell cycle regulators such as Cyclin D1, p53, p21(cip1/waf1), p19(ARF) and p16. Amongst the Jun proteins, c-Jun is unique in its ability to positively regulate cell proliferation through the repression of tumor suppressor gene expression and function, and induction of cyclin D1 transcription. These actions are antagonized by JunB, which upregulates tumor suppressor genes and represses cyclin D1. An especially important target for AP-1 effects on cell life and death is the tumor suppressor p53, whose expression as well as transcriptional activity, are modulated by AP-1 proteins.read more
Citations
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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
Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases
Marie Cargnello,Philippe P. Roux +1 more
TL;DR: The mechanisms of MAPKAPK activation by the different MAPKs are reviewed and their physiological roles based on established substrates and recent discoveries are discussed.
Journal ArticleDOI
AP-1: a double-edged sword in tumorigenesis
Robert Eferl,Erwin F. Wagner +1 more
TL;DR: This work focuses on the JUN and FOS proteins and aims to offer a new perspective on the molecular mechanisms that regulate the oncogenic and anti-oncogenic effects of AP-1 in tumour development.
Journal ArticleDOI
The Role of Oxidative Stress in Carcinogenesis
TL;DR: This review examines the evidence of cellular oxidants' involvement in the carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species.
Journal ArticleDOI
RHO-GTPases and cancer.
TL;DR: The RAS oncogenes are members of a large family of small GTPases that bind GTP and hydrolyse it to GDP and the switching between these two states regulates a wide range of cellular processes.
References
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Journal ArticleDOI
Surfing the p53 network
TL;DR: The p53 tumour-suppressor gene integrates numerous signals that control cell life and death, and the disruption of p53 has severe consequences when a highly connected node in the Internet breaks down.
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Cancer Cell Cycles
TL;DR: Genetic alterations affecting p16INK4a and cyclin D1, proteins that govern phosphorylation of the retinoblastoma protein and control exit from the G1 phase of the cell cycle, are so frequent in human cancers that inactivation of this pathway may well be necessary for tumor development.
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.
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