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Senescence of human fibroblasts induced by oncogenic Raf.
It is concluded that the kinase cascade initiated by Raf can regulate the expression of p16(Ink4a) and the proliferative arrest and senescence that follows and may provide a defense against neoplastic transformation when the MAP kinase signaling cascade is inappropriately active.
Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1
- D. Woods, D. Parry, H. Cherwinski, E. Bosch, E. Lees, M. McMahon
- BiologyMolecular and cellular biology
- 1 September 1997
The ability of Raf to elicit cell cycle arrest is strongly associated with its ability to induce the expression of the cyclin-dependent kinase inhibitor p21Cip1 in a manner that bears analogy to alpha-factor arrest in Saccharomyces cerevisiae.
Opposing Effects of Ras on p53 Transcriptional Activation of mdm2 and Induction of p19ARF
Phosphorylation of HDM2 by Akt
It is shown that HDM2 associated with the serine-threonine kinase, Akt, in response to growth factor stimulation of human primary cells, and this association was concurrent with phosphorylation of Akt (at Ser 473), and resulted in elevated expression ofHDM2 and enhanced nuclear localization.
Regulation of p53 function.
C-Terminal Ubiquitination of p53 Contributes to Nuclear Export
- M. Lohrum, D. Woods, R. Ludwig, E. Balint, K. Vousden
- BiologyMolecular and Cellular Biology
- 15 December 2001
It is shown that ubiquitination of the C terminus of p53 by MDM2 contributes to the efficient export of p 53 from the nucleus to the cytoplasm, and that nuclear export was not essential for p53 degradation.
Ras-induced serine phosphorylation of the focal adhesion protein paxillin is mediated by the Raf-->MEK-->ERK pathway.
Induction of β3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf–MEK–Extracellular Signal-Regulated Kinase Signaling Pathway
It is demonstrated that the Ras-activated Raf–MEK–extracellular signal-regulated kinase (ERK) signaling pathway can specifically control the expression of individual integrin subunits in a variety of human and mouse cell lines, and oncogene-induced alterations in integrin gene expression may participate in the changes in cell adhesion and migration that accompany the process of oncogenic transformation.
Assay for Ubiquitin Ligase Activity: High-Throughput Screen for Inhibitors of HDM2
An assay for the autoubiquitination activity of the E3 ligaseHDM2 (Mdm2), developed and adapted to a high-throughput format to identify inhibitors of this activity, may be useful in finding both inhibitors and activators of a wide range of different ubiquitin ligases.
A conditional form of Bruton's tyrosine kinase is sufficient to activate multiple downstream signaling pathways via PLC Gamma 2 in B cells
These data suggest that Btk:ER regulates downstream signaling pathways primarily via PLCγ2 in B cells, and will likely facilitate the dissection of the role of Btk and its family members in a variety of biological processes in many different cell types.