An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR
Abstract The RNA-binding protein HuR regulates various cellular processes, such as proliferation, differentiation, and cell fate. Moreover, recent studies have shown that HuR modulates the expression of factors important for tumor growth and progression. Despite its prominent role in tumorigenesis,...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-12-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-024-02268-w |
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| author | Bianca Colalillo Sujitha Sali Ali H. Aldouhki Isabelle Aubry Sergio Di Marco Michel L. Tremblay Imed E. Gallouzi |
| author_facet | Bianca Colalillo Sujitha Sali Ali H. Aldouhki Isabelle Aubry Sergio Di Marco Michel L. Tremblay Imed E. Gallouzi |
| author_sort | Bianca Colalillo |
| collection | DOAJ |
| description | Abstract The RNA-binding protein HuR regulates various cellular processes, such as proliferation, differentiation, and cell fate. Moreover, recent studies have shown that HuR modulates the expression of factors important for tumor growth and progression. Despite its prominent role in tumorigenesis, until recently, there have been no reported mutations in HuR that have been associated to cancer. Here, we show that a HuR mutation, HuR-V225I, previously identified in a patient with Adult T-cell Leukemia/Lymphoma, interferes with the pro-apoptotic function of HuR. In response to apoptosis, HuR translocates to the cytoplasm and is cleaved in a caspase-dependent manner. In cervical cancer cells, neuroblastoma cells, and T-lymphocytes, we observed a decrease in cleavage of the HuR-V225I mutant under apoptotic conditions. This effect was shown to be mediated by the nuclear retention of HuR-V225I. Finally, expression of the HuR-V225I mutant decreases the cell’s response to apoptotic stimuli through the increased expression of mRNAs encoding anti-apoptotic factors, such as XIAP and BCL-2. Therefore, our data establishes that the absence of HuR cytoplasmic translocation and cleavage promotes cell viability, and that acquiring this mutation during tumorigenesis may thus reduce the efficacy of cancer therapy. |
| format | Article |
| id | doaj-art-623e6064c4024d06a01a741d52ac8f1f |
| institution | OA Journals |
| issn | 2058-7716 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-623e6064c4024d06a01a741d52ac8f1f2025-08-20T02:31:48ZengNature Publishing GroupCell Death Discovery2058-77162024-12-0110111010.1038/s41420-024-02268-wAn HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuRBianca Colalillo0Sujitha Sali1Ali H. Aldouhki2Isabelle Aubry3Sergio Di Marco4Michel L. Tremblay5Imed E. Gallouzi6Department of Biochemistry, McGill UniversityKAUST Smart-Health Initiative and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST)KAUST Smart-Health Initiative and Biological and Environmental Science and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST)Rosalind & Morris Goodman Cancer Institute, McGill UniversityDepartment of Biochemistry, McGill UniversityDepartment of Biochemistry, McGill UniversityDepartment of Biochemistry, McGill UniversityAbstract The RNA-binding protein HuR regulates various cellular processes, such as proliferation, differentiation, and cell fate. Moreover, recent studies have shown that HuR modulates the expression of factors important for tumor growth and progression. Despite its prominent role in tumorigenesis, until recently, there have been no reported mutations in HuR that have been associated to cancer. Here, we show that a HuR mutation, HuR-V225I, previously identified in a patient with Adult T-cell Leukemia/Lymphoma, interferes with the pro-apoptotic function of HuR. In response to apoptosis, HuR translocates to the cytoplasm and is cleaved in a caspase-dependent manner. In cervical cancer cells, neuroblastoma cells, and T-lymphocytes, we observed a decrease in cleavage of the HuR-V225I mutant under apoptotic conditions. This effect was shown to be mediated by the nuclear retention of HuR-V225I. Finally, expression of the HuR-V225I mutant decreases the cell’s response to apoptotic stimuli through the increased expression of mRNAs encoding anti-apoptotic factors, such as XIAP and BCL-2. Therefore, our data establishes that the absence of HuR cytoplasmic translocation and cleavage promotes cell viability, and that acquiring this mutation during tumorigenesis may thus reduce the efficacy of cancer therapy.https://doi.org/10.1038/s41420-024-02268-w |
| spellingShingle | Bianca Colalillo Sujitha Sali Ali H. Aldouhki Isabelle Aubry Sergio Di Marco Michel L. Tremblay Imed E. Gallouzi An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR Cell Death Discovery |
| title | An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR |
| title_full | An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR |
| title_fullStr | An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR |
| title_full_unstemmed | An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR |
| title_short | An HuR mutant, HuR-V225I, identified in adult T-cell Leukemia/Lymphoma, alters the pro-apoptotic function of HuR |
| title_sort | hur mutant hur v225i identified in adult t cell leukemia lymphoma alters the pro apoptotic function of hur |
| url | https://doi.org/10.1038/s41420-024-02268-w |
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