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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...

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Autores principales: Li, Dan, Neo, Suat Peng, Gunaratne, Jayantha, Sabapathy, Kanaga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2023
Materias:
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.
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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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