JNK1 and JNK2 oppositely regulate p53 in signaling linked to apoptosis triggered by an altered fibronectin matrix: JNK links FAK and p53.
The extracellular matrix regulates many cellular processes, including survival, and alterations in the matrix or in matrix survival signals can trigger apoptosis. Previously, we showed that an altered fibronectin matrix triggers apoptosis in primary cells via a novel pathway regulated by transcriptionally mediated decreases in p53 and c-Myc levels. Here we report that this apoptotic mechanism is propagated by decreased phosphorylation of focal adhesion kinase (FAK), which is linked to increased phosphorylation of c-Jun N-terminal kinase (JNK) and to decreased levels of p53. FAK is physically and spatially linked to JNK and p53, which relocalize from the nucleus to the cell membrane to mediate this interaction. Further, p53 participates in a feedback mechanism with JNK to regulate this apoptotic process and is oppositely regulated by JNK1 and JNK2.
Tafolla
Elizabeth
E
Department of Stomatology, School of Dentistry, University of California, San Francisco, 94143-0512, USA.
Wang
Shaohui
S
Wong
Benita
B
Leong
Jeffrey
J
Kapila
Yvonne L
YL
D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D005246:Feedback; D005353:Fibronectins / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D005353:Fibronectins; D020319:Oligodeoxyribonucleotides, Antisense; D016159:Tumor Suppressor Protein p53; D048056:Mitogen-Activated Protein Kinase 9; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D048055:Mitogen-Activated Protein Kinase 8