KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems
Abstract Like other KCTD proteins, KCTD15 is involved in important albeit distinct biological processes as cancer, neural crest formation, and obesity. Here, we characterized the role of KCTD15 in different physiological/pathological states to gain insights into its diversified function(s). The sile...
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Nature Portfolio
2021
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oai:doaj.org-article:fa0ca22740494c77810ada74d6a4b4ba2021-12-02T18:02:23ZKCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems10.1038/s41598-021-97775-62045-2322https://doaj.org/article/fa0ca22740494c77810ada74d6a4b4ba2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97775-6https://doaj.org/toc/2045-2322Abstract Like other KCTD proteins, KCTD15 is involved in important albeit distinct biological processes as cancer, neural crest formation, and obesity. Here, we characterized the role of KCTD15 in different physiological/pathological states to gain insights into its diversified function(s). The silencing of KCTD15 in MLL-rearranged leukemia models induced attenuation of the NF-κB pathway associated with a downregulation of pIKK-β and pIKB-α. Conversely, the activation of peripheral blood T cells upon PMA/ionomycin stimulation remarkably upregulated KCTD15 and, simultaneously, pIKK-β and pIKB-α. Moreover, a significant upregulation of KCTD15 was also observed in CD34 hematopoietic stem/progenitor cells where the NF-κB pathway is physiologically activated. The association between KCTD15 upregulation and increased NF-κB signaling was confirmed by luciferase assay as well as KCTD15 and IKK-β proximity ligation and immunoprecipitation experiments. The observed upregulation of IKK-β by KCTD15 provides a novel and intriguing interpretative key for understanding the protein function in a wide class of physiological/pathological conditions ranging from neuronal development to cancer and obesity/diabetes.Giovanni SmaldoneLuigi CoppolaKatia PaneMonica FranzeseGiuliana BeneduceRosanna ParasoleGiuseppe MennaLuigi VitaglianoMarco SalvatorePeppino MirabelliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
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Medicine R Science Q Giovanni Smaldone Luigi Coppola Katia Pane Monica Franzese Giuliana Beneduce Rosanna Parasole Giuseppe Menna Luigi Vitagliano Marco Salvatore Peppino Mirabelli KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems |
| description |
Abstract Like other KCTD proteins, KCTD15 is involved in important albeit distinct biological processes as cancer, neural crest formation, and obesity. Here, we characterized the role of KCTD15 in different physiological/pathological states to gain insights into its diversified function(s). The silencing of KCTD15 in MLL-rearranged leukemia models induced attenuation of the NF-κB pathway associated with a downregulation of pIKK-β and pIKB-α. Conversely, the activation of peripheral blood T cells upon PMA/ionomycin stimulation remarkably upregulated KCTD15 and, simultaneously, pIKK-β and pIKB-α. Moreover, a significant upregulation of KCTD15 was also observed in CD34 hematopoietic stem/progenitor cells where the NF-κB pathway is physiologically activated. The association between KCTD15 upregulation and increased NF-κB signaling was confirmed by luciferase assay as well as KCTD15 and IKK-β proximity ligation and immunoprecipitation experiments. The observed upregulation of IKK-β by KCTD15 provides a novel and intriguing interpretative key for understanding the protein function in a wide class of physiological/pathological conditions ranging from neuronal development to cancer and obesity/diabetes. |
| format |
article |
| author |
Giovanni Smaldone Luigi Coppola Katia Pane Monica Franzese Giuliana Beneduce Rosanna Parasole Giuseppe Menna Luigi Vitagliano Marco Salvatore Peppino Mirabelli |
| author_facet |
Giovanni Smaldone Luigi Coppola Katia Pane Monica Franzese Giuliana Beneduce Rosanna Parasole Giuseppe Menna Luigi Vitagliano Marco Salvatore Peppino Mirabelli |
| author_sort |
Giovanni Smaldone |
| title |
KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems |
| title_short |
KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems |
| title_full |
KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems |
| title_fullStr |
KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems |
| title_full_unstemmed |
KCTD15 deregulation is associated with alterations of the NF-κB signaling in both pathological and physiological model systems |
| title_sort |
kctd15 deregulation is associated with alterations of the nf-κb signaling in both pathological and physiological model systems |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/fa0ca22740494c77810ada74d6a4b4ba |
| work_keys_str_mv |
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| _version_ |
1718378905411256320 |