Journal ArticleDOI
Nucleolar Arf sequesters Mdm2 and activates p53.
Jason D. Weber,Jason D. Weber,Laura J. Taylor,Martine F. Roussel,Charles J. Sherr,Dafna Bar-Sagi,Dafna Bar-Sagi +6 more
TLDR
It is shown that Arf binds to the product of the Mdm2 gene and sequesters it into the nucleolus, thereby preventing negative-feedback regulation of p53 by MDM2 and leading to the activation of p 53 in the nucleoplasm.Abstract:
The Ink4/Arf locus encodes two tumour-suppressor proteins, p16Ink4a and p19Arf, that govern the antiproliferative functions of the retinoblastoma and p53 proteins, respectively. Here we show that Arf binds to the product of the Mdm2 gene and sequesters it into the nucleolus, thereby preventing negative-feedback regulation of p53 by Mdm2 and leading to the activation of p53 in the nucleoplasm. Arf and Mdm2 co-localize in the nucleolus in response to activation of the oncoprotein Myc and as mouse fibroblasts undergo replicative senescence. These topological interactions of Arf and Mdm2 point towards a new mechanism for p53 activation.read more
Citations
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Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells.
In-Kyung Park,Dalong Qian,Mark J. Kiel,Michael W. Becker,Michael Pihalja,Irving L. Weissman,Sean J. Morrison,Sean J. Morrison,Michael F. Clarke +8 more
TL;DR: The results indicate that Bmi-1 is essential for the generation of self-renewing adult HSCs, which are required for haematopoiesis to persist for the lifetime of the animal.
Journal ArticleDOI
Requirement of JNK for Stress- Induced Activation of the Cytochrome c-Mediated Death Pathway
Cathy Tournier,Patricia M. Hess,Derek D. Yang,Jie Xu,Tod K. Turner,Anjaruwee S. Nimnual,Dafna Bar-Sagi,Stephen N. Jones,Richard A. Flavell,Roger J. Davis +9 more
TL;DR: It is shown here that JNK is required for UV-induced apoptosis in primary murine embryonic fibroblasts, and data indicate that mitochondria are influenced by proapoptotic signal transduction through the JNK pathway.
Journal ArticleDOI
Modes of p53 regulation.
Jan Philipp Kruse,Wei Gu +1 more
TL;DR: It is proposed that antirepression, the release of p53 from repression by factors such as Mdm2 and MdmX, is a key step in the physiological activation of p 53.
Journal ArticleDOI
The hallmarks of cancer: a long non-coding RNA point of view.
Tony Gutschner,Sven Diederichs +1 more
TL;DR: Here, the cellular processes influenced by long ncRNAs to the hallmarks of cancer are linked and therefore, an ncRNA point-of-view on tumor biology is provided.
Journal Article
The Pezcoller lecture: cancer cell cycles revisited.
TL;DR: Lesions in the p16--cyclin D-CDK4--Rb and ARF--Mdm2--p53 pathways occur so frequently in cancer, regardless of patient age or tumor type, that they appear to be part of the life history of most, if not all, cancer cells.
References
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
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Regulation of p53 stability by Mdm2
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