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Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells

Lipin-1 is a protein that has dual functions as a phosphatidic acid phosphohydrolase (PAP) and a nuclear transcriptional coactivator. It remains unknown how the nuclear localization and coactivator functions of lipin-1 are regulated. Here, we show that lipin-1 (including both the alpha and beta isof...

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Autores principales: Liu, Guang-Hui, Gerace, Larry
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737637/
https://www.ncbi.nlm.nih.gov/pubmed/19753306
http://dx.doi.org/10.1371/journal.pone.0007031
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author Liu, Guang-Hui
Gerace, Larry
author_facet Liu, Guang-Hui
Gerace, Larry
author_sort Liu, Guang-Hui
collection PubMed
description Lipin-1 is a protein that has dual functions as a phosphatidic acid phosphohydrolase (PAP) and a nuclear transcriptional coactivator. It remains unknown how the nuclear localization and coactivator functions of lipin-1 are regulated. Here, we show that lipin-1 (including both the alpha and beta isoforms) is modified by sumoylation at two consensus sumoylation sites. We are unable to detect sumoylation of the related proteins lipin-2 and lipin-3. Lipin-1 is sumoylated at relatively high levels in brain, where lipin-1α is the predominant form. In cultured embryonic cortical neurons and SH-SY5Y neuronal cells, ectopically expressed lipin-1α is localized in both the nucleus and the cytoplasm, and the nuclear localization is abrogated by mutating the consensus sumyolation motifs. The sumoylation site mutant of lipin-1α loses the capacity to coactivate the transcriptional (co-) activators PGC-1α and MEF2, consistent with its nuclear exclusion. Thus, these results show that sumoylation facilitates the nuclear localization and transcriptional coactivator behavior of lipin-1α that we observe in cultured neuronal cells, and suggest that lipin-1α may act as a sumoylation-regulated transcriptional coactivator in brain.
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spelling pubmed-27376372009-09-15 Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells Liu, Guang-Hui Gerace, Larry PLoS One Research Article Lipin-1 is a protein that has dual functions as a phosphatidic acid phosphohydrolase (PAP) and a nuclear transcriptional coactivator. It remains unknown how the nuclear localization and coactivator functions of lipin-1 are regulated. Here, we show that lipin-1 (including both the alpha and beta isoforms) is modified by sumoylation at two consensus sumoylation sites. We are unable to detect sumoylation of the related proteins lipin-2 and lipin-3. Lipin-1 is sumoylated at relatively high levels in brain, where lipin-1α is the predominant form. In cultured embryonic cortical neurons and SH-SY5Y neuronal cells, ectopically expressed lipin-1α is localized in both the nucleus and the cytoplasm, and the nuclear localization is abrogated by mutating the consensus sumyolation motifs. The sumoylation site mutant of lipin-1α loses the capacity to coactivate the transcriptional (co-) activators PGC-1α and MEF2, consistent with its nuclear exclusion. Thus, these results show that sumoylation facilitates the nuclear localization and transcriptional coactivator behavior of lipin-1α that we observe in cultured neuronal cells, and suggest that lipin-1α may act as a sumoylation-regulated transcriptional coactivator in brain. Public Library of Science 2009-09-15 /pmc/articles/PMC2737637/ /pubmed/19753306 http://dx.doi.org/10.1371/journal.pone.0007031 Text en Liu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liu, Guang-Hui
Gerace, Larry
Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells
title Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells
title_full Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells
title_fullStr Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells
title_full_unstemmed Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells
title_short Sumoylation Regulates Nuclear Localization of Lipin-1α in Neuronal Cells
title_sort sumoylation regulates nuclear localization of lipin-1α in neuronal cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2737637/
https://www.ncbi.nlm.nih.gov/pubmed/19753306
http://dx.doi.org/10.1371/journal.pone.0007031
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