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EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration
Polyamines promote cellular proliferation. Their levels are controlled by ornithine decarboxylase antizyme 1 (Az(1), encoded by OAZ1), through the proteasome-mediated, ubiquitin-independent degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis. Az(1)-mediat...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281260/ https://www.ncbi.nlm.nih.gov/pubmed/37325974 http://dx.doi.org/10.1242/jcs.260427 |
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author | Li, Dan Neo, Suat Peng Gunaratne, Jayantha Sabapathy, Kanaga |
author_facet | Li, Dan Neo, Suat Peng Gunaratne, Jayantha Sabapathy, Kanaga |
author_sort | Li, Dan |
collection | PubMed |
description | Polyamines promote cellular proliferation. Their levels are controlled by ornithine decarboxylase antizyme 1 (Az(1), encoded by OAZ1), through the proteasome-mediated, ubiquitin-independent degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis. Az(1)-mediated degradation of other substrates such as cyclin D1 (CCND1), DNp73 (TP73) or Mps1 regulates cell growth and centrosome amplification, and the currently known six Az(1) substrates are all linked with tumorigenesis. To understand whether Az(1)-mediated protein degradation might play a role in regulating other cellular processes associated with tumorigenesis, we employed quantitative proteomics to identify novel Az(1) substrates. Here, we describe the identification of LIM domain and actin-binding protein 1 (LIMA1), also known as epithelial protein lost in neoplasm (EPLIN), as a new Az(1) target. Interestingly, between the two EPLIN isoforms (α and β), only EPLIN-β is a substrate of Az(1). The interaction between EPLIN-β and Az(1) appears to be indirect, and EPLIN-β is degraded by Az(1) in a ubiquitination-independent manner. Az(1) absence leads to elevated EPLIN-β levels, causing enhanced cellular migration. Consistently, higher LIMA1 levels correlate with poorer overall survival of colorectal cancer patients. Overall, this study identifies EPLIN-β as a novel Az(1) substrate regulating cellular migration. |
format | Online Article Text |
id | pubmed-10281260 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-102812602023-06-21 EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration Li, Dan Neo, Suat Peng Gunaratne, Jayantha Sabapathy, Kanaga J Cell Sci Research Article Polyamines promote cellular proliferation. Their levels are controlled by ornithine decarboxylase antizyme 1 (Az(1), encoded by OAZ1), through the proteasome-mediated, ubiquitin-independent degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis. Az(1)-mediated degradation of other substrates such as cyclin D1 (CCND1), DNp73 (TP73) or Mps1 regulates cell growth and centrosome amplification, and the currently known six Az(1) substrates are all linked with tumorigenesis. To understand whether Az(1)-mediated protein degradation might play a role in regulating other cellular processes associated with tumorigenesis, we employed quantitative proteomics to identify novel Az(1) substrates. Here, we describe the identification of LIM domain and actin-binding protein 1 (LIMA1), also known as epithelial protein lost in neoplasm (EPLIN), as a new Az(1) target. Interestingly, between the two EPLIN isoforms (α and β), only EPLIN-β is a substrate of Az(1). The interaction between EPLIN-β and Az(1) appears to be indirect, and EPLIN-β is degraded by Az(1) in a ubiquitination-independent manner. Az(1) absence leads to elevated EPLIN-β levels, causing enhanced cellular migration. Consistently, higher LIMA1 levels correlate with poorer overall survival of colorectal cancer patients. Overall, this study identifies EPLIN-β as a novel Az(1) substrate regulating cellular migration. The Company of Biologists Ltd 2023-06-16 /pmc/articles/PMC10281260/ /pubmed/37325974 http://dx.doi.org/10.1242/jcs.260427 Text en © 2023. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Li, Dan Neo, Suat Peng Gunaratne, Jayantha Sabapathy, Kanaga EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration |
title | EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration |
title_full | EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration |
title_fullStr | EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration |
title_full_unstemmed | EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration |
title_short | EPLIN-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration |
title_sort | eplin-β is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10281260/ https://www.ncbi.nlm.nih.gov/pubmed/37325974 http://dx.doi.org/10.1242/jcs.260427 |
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