Department
Sciences & Mathematics
Format of Presentation
Oral Presentation
Research Category
STEM
Description
Mediation of Doxorubicin-Induced SCUBE3 Nuclear Localization by A Functional NLS Involved in Pro-Tumorigenic Actions in Breast Cancer.
Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is a glycosylated secreted and cell membrane-associated protein considered a signature gene in cancers and known to mediate its actions in the cytoplasm where its localizes prior to its secretion. However, our study observed that SCUBE3 protein localized to the nucleus following doxorubicin (DOX) treatment. In this study, we investigated SCUBE3 nuclear localization in triple-negative breast cancer, intending to dissect the mechanism of its nuclear trafficking induced by DOX treatment. Bioinformatic analysis of the SCUBE3 protein sequence with PSORTII and NLStradamus identified two different candidate nuclear localization sequences (NLS) at 532- RKGKGRRARTPP-543 (referred to as NLS-1) and 836-PPPKRKILIV-845 (referred to as NLS-2) within SCUBE3 domain. The mutagenesis of the NLS-1 abolished SCUBE3 nuclear import in the presence of DOX treatment. Consequently, mutation of the NLS-1 resulted in a significant reduction in the percent number of viable cells following DOX treatment compared to the cells transfected with the control or wild-type constructs. Altogether, these data show for the first time that SCUBE3 has a functional NLS and actively localizes into the nucleus by a classical nuclear import mechanism involving the formation of SCUBE3 complexes with importin-α. The localization of SCUBE3 to the nucleus promotes cell survival in TNBC cells.
Recommended Citation
Ilesanmi, Ayooluwa, "Doxorubicin-Induced Nuclear Localization of SCUBE3 Essential for Cell Survival in TNBC" (2024). Undergraduate Research Conference. 1.
https://athenacommons.muw.edu/urc/2024/oral-presentations-ii/1
Included in
Doxorubicin-Induced Nuclear Localization of SCUBE3 Essential for Cell Survival in TNBC
Mediation of Doxorubicin-Induced SCUBE3 Nuclear Localization by A Functional NLS Involved in Pro-Tumorigenic Actions in Breast Cancer.
Signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) is a glycosylated secreted and cell membrane-associated protein considered a signature gene in cancers and known to mediate its actions in the cytoplasm where its localizes prior to its secretion. However, our study observed that SCUBE3 protein localized to the nucleus following doxorubicin (DOX) treatment. In this study, we investigated SCUBE3 nuclear localization in triple-negative breast cancer, intending to dissect the mechanism of its nuclear trafficking induced by DOX treatment. Bioinformatic analysis of the SCUBE3 protein sequence with PSORTII and NLStradamus identified two different candidate nuclear localization sequences (NLS) at 532- RKGKGRRARTPP-543 (referred to as NLS-1) and 836-PPPKRKILIV-845 (referred to as NLS-2) within SCUBE3 domain. The mutagenesis of the NLS-1 abolished SCUBE3 nuclear import in the presence of DOX treatment. Consequently, mutation of the NLS-1 resulted in a significant reduction in the percent number of viable cells following DOX treatment compared to the cells transfected with the control or wild-type constructs. Altogether, these data show for the first time that SCUBE3 has a functional NLS and actively localizes into the nucleus by a classical nuclear import mechanism involving the formation of SCUBE3 complexes with importin-α. The localization of SCUBE3 to the nucleus promotes cell survival in TNBC cells.