|
|
|
|
|
|
|
|
|
|
Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: (02)00442-8h.htm (shortcode: fig004wkg); 25 April 2002
Reprint/PDF version Back
to main article
Multi-layered connections between the ERK pathway, the cell cycle and tumour suppressor genes
Walter Kolch, Ashwin
Kotwaliwale, Keith Vass and Petra Janosch
Author
contact details
Figure 4. Multi-layered connections between the ERK pathway, the cell cycle and tumour suppressor genes. This pathway can stimulate both cell-cycle progression and arrest. (a) Under physiological conditions, mitogen stimulation activates the pathway, inducing the expression of cyclinD and leading to the functional inactivation of the retinoblastoma (Rb) protein. (b) When the pathway is unduly hyperactivated (e.g. owing to Ras mutations), p53 is stabilised, which induces apoptosis or prevents cell-cycle progression by stimulating the expression of the cyclin-dependent kinase (CDK) inhibitor (CKI) p21waf/cip. p53 stabilisation can be achieved in several ways, including the induction of ARF (which inhibits Mdm2-induced p53 degradation) by the ERK pathway or by E2F transcription factors released from inactivated Rb. Thus, the response to genetic damage is crucially determined by p53. In cells where (c) Rb or (d) ARF functions are lost, the cell cycle can therefore proceed regardless of genetic damage or proper mitogenic stimulation (fig004wkg).
|
home | search
| glossary
| links
| sitemap | contact
|
Expert Reviews in
Molecular Medicine © Cambridge University
Press ISSN 1462-3994 (Disclaimer
and copyright)
Editorial Office: Centre for Applied Research
in Educational Technologies (CARET), 1st Floor, 16 Mill Lane, Cambridge,
CB2 1SB, UK. Tel: +44 (0)1223 765 375; Fax: +44(0)1223 765 505; E-mail: ermm@caret.cam.ac.uk