Nucleolar release of Hand1 acts as a molecular switch to determine cell fate.
The bHLH transcription factor Hand1 is essential for placentation and cardiac morphogenesis in the developing embryo. Here we implicate Hand1 as a molecular switch that determines whether a trophoblast stem cell continues to proliferate or commits to differentiation. We identify a novel interaction...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1826262211978330112 |
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| author | Martindill, D Risebro, C Smart, N Franco-Viseras, M Rosario, C Swallow, C Dennis, J Riley, P |
| author_facet | Martindill, D Risebro, C Smart, N Franco-Viseras, M Rosario, C Swallow, C Dennis, J Riley, P |
| author_sort | Martindill, D |
| collection | OXFORD |
| description | The bHLH transcription factor Hand1 is essential for placentation and cardiac morphogenesis in the developing embryo. Here we implicate Hand1 as a molecular switch that determines whether a trophoblast stem cell continues to proliferate or commits to differentiation. We identify a novel interaction of Hand1 with a protein that contains an I-mfa (inhibitor of myogenic factor) domain that anchors Hand1 in the nucleolus where it negatively regulates Hand1 activity. In the trophoblast stem-cell line Rcho-1, nucleolar sequestration of Hand1 accompanies sustained cell proliferation and renewal, whereas release of Hand1 into the nucleus leads to its activation, thus committing cells to a differentiated giant-cell fate. Site-specific phosphorylation is required for nucleolar release of Hand1, for its dimerization and biological function, and this is mediated by the non-canonical polo-like kinase Plk4 (Sak). Sak is co-expressed in Rcho-1 cells, localizes to the nucleolus during G2 and phosphorylates Hand1 as a requirement for trophoblast stem-cell commitment to a giant-cell fate. This study defines a novel cellular mechanism for regulating Hand1 that is a crucial step in the stem-cell differentiation pathway. |
| first_indexed | 2024-03-06T19:32:49Z |
| format | Journal article |
| id | oxford-uuid:1e0e668d-7f37-4144-8d40-3f856022c66e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:32:49Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:1e0e668d-7f37-4144-8d40-3f856022c66e2022-03-26T11:14:14ZNucleolar release of Hand1 acts as a molecular switch to determine cell fate.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1e0e668d-7f37-4144-8d40-3f856022c66eEnglishSymplectic Elements at Oxford2007Martindill, DRisebro, CSmart, NFranco-Viseras, MRosario, CSwallow, CDennis, JRiley, PThe bHLH transcription factor Hand1 is essential for placentation and cardiac morphogenesis in the developing embryo. Here we implicate Hand1 as a molecular switch that determines whether a trophoblast stem cell continues to proliferate or commits to differentiation. We identify a novel interaction of Hand1 with a protein that contains an I-mfa (inhibitor of myogenic factor) domain that anchors Hand1 in the nucleolus where it negatively regulates Hand1 activity. In the trophoblast stem-cell line Rcho-1, nucleolar sequestration of Hand1 accompanies sustained cell proliferation and renewal, whereas release of Hand1 into the nucleus leads to its activation, thus committing cells to a differentiated giant-cell fate. Site-specific phosphorylation is required for nucleolar release of Hand1, for its dimerization and biological function, and this is mediated by the non-canonical polo-like kinase Plk4 (Sak). Sak is co-expressed in Rcho-1 cells, localizes to the nucleolus during G2 and phosphorylates Hand1 as a requirement for trophoblast stem-cell commitment to a giant-cell fate. This study defines a novel cellular mechanism for regulating Hand1 that is a crucial step in the stem-cell differentiation pathway. |
| spellingShingle | Martindill, D Risebro, C Smart, N Franco-Viseras, M Rosario, C Swallow, C Dennis, J Riley, P Nucleolar release of Hand1 acts as a molecular switch to determine cell fate. |
| title | Nucleolar release of Hand1 acts as a molecular switch to determine cell fate. |
| title_full | Nucleolar release of Hand1 acts as a molecular switch to determine cell fate. |
| title_fullStr | Nucleolar release of Hand1 acts as a molecular switch to determine cell fate. |
| title_full_unstemmed | Nucleolar release of Hand1 acts as a molecular switch to determine cell fate. |
| title_short | Nucleolar release of Hand1 acts as a molecular switch to determine cell fate. |
| title_sort | nucleolar release of hand1 acts as a molecular switch to determine cell fate |
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