The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis.
BACKGROUND: NORE1A and RASSF1A are growth and tumour suppressors inactivated in a variety of cancers. Methylation of NORE1A and RASSF1A promoters is the predominant mechanism for downregulation of these proteins; however, other mechanisms are likely to exist. METHODOLOGY/PRINCIPAL FINDINGS: Here we...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2602596?pdf=render |
| _version_ | 1818230225570365440 |
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| author | Sergey Kuznetsov Andrei V Khokhlatchev |
| author_facet | Sergey Kuznetsov Andrei V Khokhlatchev |
| author_sort | Sergey Kuznetsov |
| collection | DOAJ |
| description | BACKGROUND: NORE1A and RASSF1A are growth and tumour suppressors inactivated in a variety of cancers. Methylation of NORE1A and RASSF1A promoters is the predominant mechanism for downregulation of these proteins; however, other mechanisms are likely to exist. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a proteolysis of NORE1A and RASSF1A by calpains as alternative mechanism of their downregulation. Extracts of H358 cell line, a human bronchoalveolar carcinoma, and H460, a large cell carcinoma, were capable of proteolysis of NORE1A protein in the calpain-dependent manner. Likewise, RASSF1A tumor suppressor was proteolyzed by the H358 cell extract. Addition of calpain inhibitor to H358 and H460 cells growing in tissue culture resulted in re-expression of endogenous NORE1A. A survey of 10 human lung tumours revealed that three of them contain an activity capable of inducing NORE1A degradation. CONCLUSIONS/SIGNIFICANCE: Thus, degradation by calpains is a novel mechanism for downregulation of NORE1A and RASSF1A proteins and might be the mechanism allowing cancer cells to escape growth suppression. |
| first_indexed | 2024-12-12T10:31:07Z |
| format | Article |
| id | doaj.art-773922b6a2f247a88fbc489313740d20 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T10:31:07Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-773922b6a2f247a88fbc489313740d202022-12-22T00:27:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01312e399710.1371/journal.pone.0003997The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis.Sergey KuznetsovAndrei V KhokhlatchevBACKGROUND: NORE1A and RASSF1A are growth and tumour suppressors inactivated in a variety of cancers. Methylation of NORE1A and RASSF1A promoters is the predominant mechanism for downregulation of these proteins; however, other mechanisms are likely to exist. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a proteolysis of NORE1A and RASSF1A by calpains as alternative mechanism of their downregulation. Extracts of H358 cell line, a human bronchoalveolar carcinoma, and H460, a large cell carcinoma, were capable of proteolysis of NORE1A protein in the calpain-dependent manner. Likewise, RASSF1A tumor suppressor was proteolyzed by the H358 cell extract. Addition of calpain inhibitor to H358 and H460 cells growing in tissue culture resulted in re-expression of endogenous NORE1A. A survey of 10 human lung tumours revealed that three of them contain an activity capable of inducing NORE1A degradation. CONCLUSIONS/SIGNIFICANCE: Thus, degradation by calpains is a novel mechanism for downregulation of NORE1A and RASSF1A proteins and might be the mechanism allowing cancer cells to escape growth suppression.http://europepmc.org/articles/PMC2602596?pdf=render |
| spellingShingle | Sergey Kuznetsov Andrei V Khokhlatchev The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. PLoS ONE |
| title | The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. |
| title_full | The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. |
| title_fullStr | The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. |
| title_full_unstemmed | The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. |
| title_short | The growth and tumor suppressors NORE1A and RASSF1A are targets for calpain-mediated proteolysis. |
| title_sort | growth and tumor suppressors nore1a and rassf1a are targets for calpain mediated proteolysis |
| url | http://europepmc.org/articles/PMC2602596?pdf=render |
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