Sumoylation regulates nuclear localization of lipin-1alpha 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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-09-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2737637?pdf=render |
| _version_ | 1828446617495142400 |
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| author | Guang-Hui Liu Larry Gerace |
| author_facet | Guang-Hui Liu Larry Gerace |
| author_sort | Guang-Hui Liu |
| collection | DOAJ |
| 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-1alpha is the predominant form. In cultured embryonic cortical neurons and SH-SY5Y neuronal cells, ectopically expressed lipin-1alpha 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-1alpha loses the capacity to coactivate the transcriptional (co-) activators PGC-1alpha and MEF2, consistent with its nuclear exclusion. Thus, these results show that sumoylation facilitates the nuclear localization and transcriptional coactivator behavior of lipin-1alpha that we observe in cultured neuronal cells, and suggest that lipin-1alpha may act as a sumoylation-regulated transcriptional coactivator in brain. |
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| format | Article |
| id | doaj.art-bc8bc0c9e412467c95878a99a62dcef0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T22:14:52Z |
| publishDate | 2009-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bc8bc0c9e412467c95878a99a62dcef02022-12-22T01:31:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-09-0149e703110.1371/journal.pone.0007031Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells.Guang-Hui LiuLarry GeraceLipin-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-1alpha is the predominant form. In cultured embryonic cortical neurons and SH-SY5Y neuronal cells, ectopically expressed lipin-1alpha 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-1alpha loses the capacity to coactivate the transcriptional (co-) activators PGC-1alpha and MEF2, consistent with its nuclear exclusion. Thus, these results show that sumoylation facilitates the nuclear localization and transcriptional coactivator behavior of lipin-1alpha that we observe in cultured neuronal cells, and suggest that lipin-1alpha may act as a sumoylation-regulated transcriptional coactivator in brain.http://europepmc.org/articles/PMC2737637?pdf=render |
| spellingShingle | Guang-Hui Liu Larry Gerace Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells. PLoS ONE |
| title | Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells. |
| title_full | Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells. |
| title_fullStr | Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells. |
| title_full_unstemmed | Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells. |
| title_short | Sumoylation regulates nuclear localization of lipin-1alpha in neuronal cells. |
| title_sort | sumoylation regulates nuclear localization of lipin 1alpha in neuronal cells |
| url | http://europepmc.org/articles/PMC2737637?pdf=render |
| work_keys_str_mv | AT guanghuiliu sumoylationregulatesnuclearlocalizationoflipin1alphainneuronalcells AT larrygerace sumoylationregulatesnuclearlocalizationoflipin1alphainneuronalcells |