We report here the identification of the homologous gene pair ZDS1,2 as multicopy suppressors of a temperature-sensitive allele (cka2-13(ts)) of the CKA2 gene encoding the alpha' catalytic subunit of protein kinase CK2. Overexpression of ZDS1,2 suppressed the temperature sensitivity, geldanamycin (GA) sensitivity, slow growth, and flocculation of multiple cka2 alleles and enhanced CK2 activity in vivo toward a known physiological substrate, Fpr3. Consistent with the existence of a recently described positive feedback loop between CK2 and Cdc37, overexpression of ZDS1,2 also suppressed the temperature sensitivity, abnormal morphology, and GA sensitivity of a CK2 phosphorylation-deficient mutant of CDC37, cdc37-S14A, as well as the GA sensitivity of a cdc37-1 allele. A likely basis for all of these effects is our observation that ZDS1,2 overexpression enhances Cdc37 protein levels. Activation of the positive feedback loop between CK2 and Cdc37 likely contributes to the pleiotropic nature of ZDS1,2, as both CK2 and Cdc37 regulate diverse cellular functions.
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http://dx.doi.org/10.1016/s0014-5793(03)01165-7 | DOI Listing |
Int J Biol Macromol
September 2024
Medical Research Institute, Southwest University, Chongqing 400715, China; State Key Laboratory of Resource Insects, Southwest University, Chongqing 400715, China; Jinfeng Laboratory, Chongqing 401329, China. Electronic address:
Protein kinase 2 (CK2) is an enzyme ubiquitously present and exhibits extensive kinase activity. It has been strongly linked to tumor progression through the abnormal phosphorylation of key proteins. Research has consistently demonstrated that CK2 is deregulated in various cancer types, with enhanced protein expression and nuclear distribution in tumor cells.
View Article and Find Full Text PDFMed Oncol
March 2024
School of Life Sciences, Jiangsu University, Zhenjiang, 212013, Jiangsu, People's Republic of China.
Casein kinase II (CK2) is an enzyme with pleiotropic kinase activity that catalyzes the phosphorylation of lots of substrates, including STAT3, p53, JAK2, PTEN, RELA, and AKT, leading to the regulation of diabetes, cardiovascular diseases, angiogenesis, and tumor progression. CK2 is observed to have high expression in multiple types of cancer, which is associated with poor prognosis. CK2 holds significant importance in the intricate network of pathways involved in promoting cell proliferation, invasion, migration, apoptosis, and tumor growth by multiple pathways such as JAK2/STAT3, PI3K/AKT, ATF4/p21, and HSP90/Cdc37.
View Article and Find Full Text PDFBiochem Biophys Res Commun
October 2020
Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/B, Padova, Italy; CNR Institute of Neuroscience, Viale G. Colombo 3, Padova, Italy. Electronic address:
Viable clones of C2C12 myoblasts where both catalytic subunits of protein kinase CK2 had been knocked out by the CRISPR/Cas9 methodology have recently been generated, thus challenging the concept that CK2 is essential for cell viability. Here we present evidence that these cells are still endowed with a residual "CK2-like" activity that is able to phosphorylate Ser-13 of endogenous CDC37. Searching for a molecular entity accounting for such an activity we have identified a band running slightly ahead of CK2α' on SDS-PAGE.
View Article and Find Full Text PDFBr J Cancer
February 2020
Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China.
Background: Most gastrointestinal stromal tumours (GIST) are driven by activating oncogenic mutations of KIT/PDGFRA, which provide a compelling therapeutic target. Our previous studies showed that CDC37, regulated by casein kinase 2 (CK2), is a crucial HSP90 cofactor for KIT oncogenic function and a promising and more selective therapeutic target in GIST.
Methods: Biologic mechanisms of CK2-mediated CDC37 regulation were assessed in GISTs by immunoblotting, immunoprecipitations, knockdown and inactivation assays.
Antioxidants (Basel)
March 2019
Faculty of Medicine, University of Tsukuba, Tsukuba Ibaraki 305-8575, Japan.
Membrane-associated estrogen receptors (ER)-α36 and G protein-coupled estrogen receptor (GPER) play important roles in the estrogen's rapid non-genomic actions including stimulation of cell proliferation. Estrogen via these receptors induces rapid activation of transcription factor nuclear factor-E2-related factor 2 (Nrf2), a master regulator of detoxification and antioxidant systems, playing a key role in the metabolic reprogramming to support cell proliferation. This review highlights the possible mechanism underlying rapid Nrf2 activation via membrane-associated estrogen receptors by estrogen and phytoestrogens.
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