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Proapoptotic fibronectin fragment induces the degradation of ubiquitinated p53 via proteasomes in periodontal ligament cells
Author(s) -
Ghosh A.,
Joo N. E.,
Chen T. C.,
Kapila Y. L.
Publication year - 2010
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.2009.01261.x
Subject(s) - mg132 , lactacystin , fibronectin , ubiquitin , apoptosis , microbiology and biotechnology , transfection , proteasome , proteasome inhibitor , extracellular matrix , chemistry , biology , cell culture , cancer research , biochemistry , genetics , gene
Ghosh A, Joo NE, ChenTC, Kapila YL. Proapoptotic fibronectin fragment induces the degradation of ubiquitinated p53 via proteasomes in periodontal ligament cells. J Periodont Res 2010; 45: 481–487. © 2010 John Wiley & Sons A/SBackground and Objective: The extracellular matrix (ECM) plays a key role in signaling necessary for tissue remodeling and cell survival. However, signals from the ECM altered by disease, e.g. inflammatory diseases such as periodontitis and arthritis, may lead to apoptosis or programmed cell death of resident cells. Previously, we found that a disease‐associated fibronectin fragment triggers apoptosis of primary human periodontal ligament cells via a novel apoptotic pathway in which the tumor suppressor, p53, is transcriptionally downregulated. Material and Methods: We used immunofluorescence, transfection assays, western blotting and ELISAs to show that p53 is degraded by a proteasomal pathway in response to a proapoptotic disease‐associated fibronectin fragment. Results: We found that in these apoptotic conditions, p53 is further downregulated by post‐translational ubiquitination and subsequent targeting to proteasomes for degradation. Pretreatment of cells with the proteasomal inhibitors MG132 and lactacystin rescued the cells from apoptosis. The p53 levels in cells transfected with ubiquitin small interfering RNA were resistant to degradation induced by the proapoptotic fibronectin fragment, showing that ubiquitination is important for the proapoptotic fibronectin fragment‐induced degradation of p53. Conclusion: These data show that a proapoptotic fibronectin matrix induces ubiquitination and degradation of p53 in the proteasome as part of a novel mechanism of apoptosis associated with inflammatory diseases.