Co-relation with novel phosphorylation sites of IκBα and necroptosis in breast cancer cells
| Autor: | Sung Hoon Choi, Shin Ae Yoo, Young Ho Chung, Sung Gil Chi, Hee Sub Yoon, Eun Hee Han, Joo Hee Park, Sung Ho Yun |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Necroptosis Cell IκBα Breast Neoplasms IκB kinase New phospho-site Serine 03 medical and health sciences Breast cancer 0302 clinical medicine Aurora kinase NF-KappaB Inhibitor alpha Tandem Mass Spectrometry Genetics medicine Humans Aurora Kinase C Phosphorylation RC254-282 Binding Sites Kinase Chemistry NF-kappa B Neoplasms. Tumors. Oncology. Including cancer and carcinogens Recombinant Proteins Cell biology 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization MCF-7 Cells Mutagenesis Site-Directed Female Research Article |
| Zdroj: | BMC Cancer BMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021) |
| ISSN: | 1471-2407 |
| Popis: | Background Phosphorylation of NF-kappaB inhibitor alpha (IκBα) is key to regulation of NF-κB transcription factor activity in the cell. Several sites of IκBα phosphorylation by members of the IκB kinase family have been identified, but phosphorylation of the protein by other kinases remains poorly understood. We investigated a new phosphorylation site on IκBα and identified its biological function in breast cancer cells. Methods Previously, we observed that aurora kinase (AURK) binds IκBα in the cell. To identify the domains of IκBα essential for phosphorylation by AURK, we performed kinase assays with a series of IκBα truncation mutants. AURK significantly promoted activation of IκBα at serine 32 but not serine 36; by contrast, IκB kinase (IKK) family proteins activated both of these residues. We also confirmed phosphorylation of IκBα by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and nano-liquid chromatography hybrid quadrupole orbitrap mass spectrometer (nanoLC-MS/MS; Q-Exactive). Results We identified two novel sites of serine phosphorylation, S63 and S262. Alanine substitution of S63 and S262 (S63A and S262A) of IκBα inhibited proliferation and suppressed p65 transcription activity. In addition, S63A and/or S262A of IκBα regulated apoptotic and necroptotic effects in breast cancer cells. Conclusions Phosphorylation of IκBα by AURK at novel sites is related to the apoptosis and necroptosis pathways in breast cancer cells. |
| Databáze: | OpenAIRE |
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