The heparin-binding domain and V region of fibronectin regulate apoptosis by suppression of p53 and c-myc in human primary cells.
In apoptosis the tumor suppressor p53 and the c-myc proto-oncogene are usually up-regulated. We show a novel alternative pathway of apoptosis in human primary cells that is mediated by transcriptionally dependent decreases in p53 and c-Myc and decreases in p21. This pathway is regulated by the alternatively spliced V region and high-affinity heparin-binding domain of fibronectin. Requirements for c-Myc, p53, and p21 signals in maintaining survival and for their decreases in inducing apoptosis were demonstrated by the ability of p53, c-Myc, and p21 ectopic expression to rescue this apoptotic phenotype, and the ability of p53-deficient and c-myc antisense conditions to trigger a faster rate of apoptosis.
Kapila
Yvonne L
YL
Department of Stomatology, School of Dentistry, University of California San Francisco, San Francisco, California 94143, USA. ykapila@itsa.ucsf.edu
Wang
Shaohui
S
Dazin
Paul
P
Tafolla
Elizabeth
E
Mass
Marc J
MJ
D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism*; D006493:Heparin / Q000737:chemistry*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D005353:Fibronectins; C000715470:MAS1 protein, human; D016376:Oligonucleotides, Antisense; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D012313:RNA; D006493:Heparin; D015500:Chloramphenicol O-Acetyltransferase; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)