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THE HEPARIN-BINDING DOMAIN AND V REGION OF FIBRONECTIN REGULATE APOPTOSIS BY SUPPRESSION OF P53 AND C-MYC IN HUMAN PRIMARY CELLS
Citation:
Kapita, Y., S. Wang, P. Dazin, E. Tafolla, AND M J. Mass. THE HEPARIN-BINDING DOMAIN AND V REGION OF FIBRONECTIN REGULATE APOPTOSIS BY SUPPRESSION OF P53 AND C-MYC IN HUMAN PRIMARY CELLS. THE JOURNAL OF BIOLOGICAL CHEMISTRY 277(10):8482-8491, (2000).
Description:
In apoptosis the tumor suppressor p53 and oncogene c-myc, are usually upregulated. However, we report here an alternate pathway of regulation that is triggered by inflammatory-associated matrix fragments of fibronectin (FN) and leads to apoptosis. It is mediated by transcriptionally-dependent decreases in p53 and c-myc, decreases in p21, and increases in bax. Requirements for c-myc, p53, and p21 signals in maintaining survival, and their requisite decreases in inducing FN fragment-triggered apoptosis were demonstrated by the ability of p53, c-myc, and p21 ectopic expression to rescue this apoptotic phenotype, and since p53-deficient and c-myc antisense conditions triggered a faster rate of apoptosis.