Journal ArticleDOI
Chemical Features of the Protein Kinase CK2 Polyamine Binding Site
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TLDR
The elaboration of the first model defining the crucial structural parameters of a polyamine-protein interaction at the molecular level is elaborated, with spermine found to be the most efficient stimulator of the kinase activity and the best CK2 ligand.Abstract:
Protein kinase CK2 is a ubiquitous eukaryotic Ser/Thr kinase whose catalytic activity is enhanced several times by polyamines. We have shown previously that the regulatory beta-subunit of CK2 bears a polyamine binding site located in the region Asp51-Tyr110. In the present study, we have used spermine analogs to investigate the structural requirements of the CK2 polyamine binding site. We have observed a strong correlation between the stimulations of CK2 activity by all tested polyamines and their binding efficiencies to the enzyme. As a result, spermine was found to be the most efficient stimulator of the kinase activity and the best CK2 ligand. The effect of the pH on the stimulation of CK2 activity by spermine strongly suggests the involvement of ionic interactions between the positive charges of spermine and the negative charges of acidic amino acids of the beta-subunit. Using a fusion protein made of MBP and the beta-subunit region encompassing amino acid residues Asp51-Pro110, we have studied the binding of spermine as a function of the ionic strength. We show that this region delineates a functional and autonomous domain containing a binding site involved in the interaction with the four positive charges of spermine. Altogether, these results led to the elaboration of the first model defining the crucial structural parameters of a polyamine-protein interaction at the molecular level.read more
Citations
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Journal ArticleDOI
Telomere dysfunction: a potential cancer predisposition factor.
Xifeng Wu,Christopher I. Amos,Yong Zhu,Hua Zhao,Barton H. Grossman,Jerry W. Shay,Sherry Luo,Waun Ki Hong,Margaret R. Spitz +8 more
TL;DR: Telomere length was statistically significantly and inversely associated with baseline and mutagen-induced genetic instability and appears to be associated with increased risks for human bladder, head and neck, lung, and renal cell cancers.
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Polyamine-dependent gene expression.
A C Childs,D J Mehta,E W Gerner +2 more
TL;DR: Several roles of polyamines in gene expression are addressed, including those used in the posttranslational modification of eukaryotic initiation factor 5A, which regulates the transport and processing of specific RNA and the novel RNA-decoding mechanism of at least two known genes.
Book ChapterDOI
Protein kinase CK2 ("casein kinase-2") and its implication in cell division and proliferation.
Lorenzo A. Pinna,Flavio Meggio +1 more
TL;DR: A number of functional features of the beta-subunit which could cooperate to the modulation of CK2 targeting/activity will be discussed.
Journal ArticleDOI
Crystal structure of the human protein kinase CK2 regulatory subunit reveals its zinc finger-mediated dimerization.
Laurent Chantalat,Didier Leroy,Odile Filhol,Arsenio Nueda,Maria Jose Benitez,Edmond M. Chambaz,Claude Cochet,Otto Dideberg +7 more
TL;DR: Interestingly, conserved amino acid residues among β subunit sequences are clustered along one linear ridge that wraps around the entire dimer, which suggests that protein partners may interact with the dimer through a stretch of residues in an extended conformation.
Journal ArticleDOI
Order or chaos? An evaluation of the regulation of protein kinase CK2.
TL;DR: This review will examine mechanisms including regulated expression and assembly of CK2 subunits, phosphorylation of CK1, and interactions with small molecules or cellular proteins that could contribute to the local regulation of distinct CK2 populations.
References
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Journal ArticleDOI
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TL;DR: Data suggest that while the casein kinase G alpha subunit bears the catalytic site, stoichiometric combination with the beta subunit is required for optimal enzymatic activity.