CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 Bodies
The cochaperone BCL2-associated athanogene 3 (BAG3), in complex with the heat shock protein HSPB8, facilitates mitotic rounding, spindle orientation, and proper abscission of daughter cells. BAG3 and HSPB8 mitotic functions implicate the sequestosome p62/SQSTM1, suggesting a role for protein quality...
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MDPI AG
2021-10-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2638 |
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| author | Carole Luthold Herman Lambert Solenn M. Guilbert Marc-Antoine Rodrigue Margit Fuchs Alice-Anaïs Varlet Amélie Fradet-Turcotte Josée N. Lavoie |
| author_facet | Carole Luthold Herman Lambert Solenn M. Guilbert Marc-Antoine Rodrigue Margit Fuchs Alice-Anaïs Varlet Amélie Fradet-Turcotte Josée N. Lavoie |
| author_sort | Carole Luthold |
| collection | DOAJ |
| description | The cochaperone BCL2-associated athanogene 3 (BAG3), in complex with the heat shock protein HSPB8, facilitates mitotic rounding, spindle orientation, and proper abscission of daughter cells. BAG3 and HSPB8 mitotic functions implicate the sequestosome p62/SQSTM1, suggesting a role for protein quality control. However, the interplay between this chaperone-assisted pathway and the mitotic machinery is not known. Here, we show that BAG3 phosphorylation at the conserved T285 is regulated by CDK1 and activates its function in mitotic cell shape remodeling. BAG3 phosphorylation exhibited a high dynamic at mitotic entry and both a non-phosphorylatable BAG3<sup>T285A</sup> and a phosphomimetic BAG3<sup>T285D</sup> protein were unable to correct the mitotic defects in BAG3-depleted HeLa cells. We also demonstrate that BAG3 phosphorylation, HSPB8, and CDK1 activity modulate the molecular assembly of p62/SQSTM1 into mitotic bodies containing K63 polyubiquitinated chains. These findings suggest the existence of a mitotically regulated spatial quality control mechanism for the fidelity of cell shape remodeling in highly dividing cells. |
| first_indexed | 2024-03-10T06:39:32Z |
| format | Article |
| id | doaj.art-6f8aa7adb1fb49bba81b2d28869a7b5c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:32Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6f8aa7adb1fb49bba81b2d28869a7b5c2023-11-22T17:46:48ZengMDPI AGCells2073-44092021-10-011010263810.3390/cells10102638CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 BodiesCarole Luthold0Herman Lambert1Solenn M. Guilbert2Marc-Antoine Rodrigue3Margit Fuchs4Alice-Anaïs Varlet5Amélie Fradet-Turcotte6Josée N. Lavoie7Centre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaCentre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaCentre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaCentre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaCentre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaCentre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaCentre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaCentre de Recherche sur le Cancer, Université Laval, Quebec, QC G1R 3S3, CanadaThe cochaperone BCL2-associated athanogene 3 (BAG3), in complex with the heat shock protein HSPB8, facilitates mitotic rounding, spindle orientation, and proper abscission of daughter cells. BAG3 and HSPB8 mitotic functions implicate the sequestosome p62/SQSTM1, suggesting a role for protein quality control. However, the interplay between this chaperone-assisted pathway and the mitotic machinery is not known. Here, we show that BAG3 phosphorylation at the conserved T285 is regulated by CDK1 and activates its function in mitotic cell shape remodeling. BAG3 phosphorylation exhibited a high dynamic at mitotic entry and both a non-phosphorylatable BAG3<sup>T285A</sup> and a phosphomimetic BAG3<sup>T285D</sup> protein were unable to correct the mitotic defects in BAG3-depleted HeLa cells. We also demonstrate that BAG3 phosphorylation, HSPB8, and CDK1 activity modulate the molecular assembly of p62/SQSTM1 into mitotic bodies containing K63 polyubiquitinated chains. These findings suggest the existence of a mitotically regulated spatial quality control mechanism for the fidelity of cell shape remodeling in highly dividing cells.https://www.mdpi.com/2073-4409/10/10/2638BAG3 1HSPB8 2p62/SQSTM1 bodies 3CDK1 4spindle positioning 5mitotic cell rounding 6 |
| spellingShingle | Carole Luthold Herman Lambert Solenn M. Guilbert Marc-Antoine Rodrigue Margit Fuchs Alice-Anaïs Varlet Amélie Fradet-Turcotte Josée N. Lavoie CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 Bodies Cells BAG3 1 HSPB8 2 p62/SQSTM1 bodies 3 CDK1 4 spindle positioning 5 mitotic cell rounding 6 |
| title | CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 Bodies |
| title_full | CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 Bodies |
| title_fullStr | CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 Bodies |
| title_full_unstemmed | CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 Bodies |
| title_short | CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 Bodies |
| title_sort | cdk1 mediated phosphorylation of bag3 promotes mitotic cell shape remodeling and the molecular assembly of mitotic p62 bodies |
| topic | BAG3 1 HSPB8 2 p62/SQSTM1 bodies 3 CDK1 4 spindle positioning 5 mitotic cell rounding 6 |
| url | https://www.mdpi.com/2073-4409/10/10/2638 |
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