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The phosphorylation of HIV-1 Rev by protein kinase CK2 is strictly dependent on the regulatory β subunit of the kinase and is deeply affected by conformational changes of the substrate outside the phosphorylation site [12]. Here we show that Rev modulates a variety of CK2 properties, including autophosphorylation, catalytic activity toward calmodulin, and susceptibility to polycationic effectors, whose common denominator is the involvement of the β subunit. Rev’s two major CK2 sites are located at its N-terminus, immediately adjacent to a helix-loop-helix motif. By comparing the behaviour of full-size Rev with that of synthetic peptides reproducing, with suitable modifications, its N-terminal 26 amino acids including the phosphoacceptor site (Ser 5, Ser 8) and amphipathic helix-1, it appears that the functional interaction of the N-terminal portion of Rev with the N-terminal domain of the β subunit must rely on both electrostatic and hydrophobic interactions. The former mainly involve Rev’s arginine-rich domain (residues 35-50) in helix-2, while the latter are mostly mediated by residues 12-24 of helix-1. These data disclose the possibility that, besides displaying protective, regulatory and targeting properties with respect to the catalytic subunit, the CK2 β subunit also plays a role as a docking site for a subset of CK2 substrates. (Mol Cell Biochem 227: 145-151, 2001)

Synthetic peptides reproducing the amino and carboxyl terminal region of CK2 β subunit have been analyzed for their ability to mimic different properties of full length β subunit. Peptide β[1–77], containing both the autophosphorylation site and the down-regulatory domain 55–l64, is readily phosphorylated by α subunit whose activity is concomitantly inhibited. Such inhibition is accompanied by a weak interaction detectable by BIAcore sensograms but not by far Western blots, and is not reversed by polylysine which conversely overcome inhibition of calmodulin phosphorylation by full length β subunit. A strong interaction with α is observed with β[155–215] but not with its shorter derivative β[170–215] as judged from far Western blotting and sucrose gradient ultracentrifugation analysis. Both peptides, however, affect the regular interaction between α and β subunits altering the autophosphorylation pattern and responsiveness to salt. β[ 155–215], unlike β[ 170–215] tends to aggregate more readily than full length β subunit. This behaviour which is reminiscent of the homodimerization of full length β subunit, would indicate that tight self-association of β[ 155–215] crucially depends on residues in the 155–170 sequence. Failure of β[1–77] fragment to mediate responsiveness to polybasic peptides and accentuated self-association propensity of β[ 155–215] suggest that other structural elements between the sequences 1–77 and 155–215 are required in order to confer optimal functionality to the β subunit. (Mol Cell Biochem 191: 35–42, 1999).

Protein kinase CK2 (also termed casein kinase-2 or -II) is a ubiquitous Ser/Thr-specific protein kinase required for viability and for cell cycle progression. CK2 is especially elevated in proliferating tissues, either normal or transformed, and the expression of its catalytic subunit in transgenic mice is causative of lymphomas. CK2 is highly pleiotropic: more than 160 proteins phosphorylated by it at sites specified by multiple acidic residues are known. Despite its heterotetrameric structure generally composed by two catalytic (α and/or α’) and two non catalytic β-subunits, the regulation of CK2 is still enigmatic. A number of functional features of the β-subunit which could cooperate to the modulation of CK2 targeting/activity will be discussed.

The regulation of ornithine decarboxylase (ODC) in mammalian cells appears to be complex and not completely clarified.1, 2 This enzyme is characterized by a very short half-life, but the mechanism of ODC degradation is as yet unknown3. Because of the rapid turnover, changes in the rate of synthesis are promptly expressed as fluctuations of ODC activity1, 4. However, a post-translational control of ODC has been proposed by several Authors1, and include interaction with a specific inhibitor, antizyme5, and interconversion between distinct charged species6. These mechanisms could account for the occurence of inactive ODC forms or play a function in the process of ODC decay, although their precise role remains to be defined. The present paper focuses on two additional covalent modifications of ODC molecule, which could cooperate at the control of ODC activity and decay: the reversible oxidation of sulphydrylic groups and the phosphorylation by a particular class of protein kinases, called casein kinase-2 (CK-2).