Distinct regulation of Ubc13 functions by the two ubiquitin-conjugating enzyme variants Mms2 and Uev1A

Ubc13, a ubiquitin-conjugating enzyme (Ubc), requires the presence of a Ubc variant (Uev) for polyubiquitination. Uevs, although resembling Ubc in sequence and structure, lack the active site cysteine residue and are catalytically inactive. The yeast Uev (Mms2) incites noncanonical Lys63-linked polyubiquitination by Ubc13, whereas the increased diversity of Uevs in higher eukaryotes suggests an unexpected complication in ubiquitination. In this study, we demonstrate that divergent activities of mammalian Ubc13 rely on its pairing with either of two Uevs, Uev1A or Mms2. Structurally, we demonstrate that Mms2 and Uev1A differentially modulate the length of Ubc13-mediated Lys63-linked polyubiquitin chains. Functionally, we describe that Ubc13–Mms2 is required for DNA damage repair but not nuclear factor κB (NF-κB) activation, whereas Ubc13–Uev1A is involved in NF-κB activation but not DNA repair. Our finding suggests a novel regulatory mechanism in which different Uevs direct Ubcs to diverse cellular processes through physical interaction and alternative polyubiquitination

Обеспечение реализации принципа законности в административно-юрисдикционной деятельности налоговой милиции

Пастушок, І. М. Забезпечення реалізації принципу законності в адміністративно-юрисдикційній діяльності податкової міліції / І. М. Пастушок // Вісник Національного університету внутрішніх справ. - 2003. - Вип. 23. - С. 155-159.Розглянуто поняття та значення принципу законності у адміністративно-юрисдикційній діяльності податкової міліції; система юридичних гарантій законності адміністративно-юрисдикційної діяльності цієї служби; шляхи підвищення ефективності засобів забезпечення законності у зазначеній сфері. The concept and significance of the principle of legality in the administrative and jurisdictional activities of the tax police are considered; system of legal guarantees of legality of administrative-jurisdictional activity of this service; ways to increase the effectiveness of legal means in this area. Рассмотрены понятие и значение принципа законности в административно-юрисдикционной деятельности налоговой милиции; система юридических гарантий законности административно-юрисдикционной деятельности этой службы; пути повышения эффективности средств обеспечения законности в указанной сфере

LH biosynthesis and secretion in rat anterior pituitary cell cultures: Stimulation of LH glycosylation and secretion by GNRH and an agonistic analogue and blockade by an antagonistic analogue

In rat anterior pituitary cell cultures GnRH (1nM) stimulated a progressive increase in LH release into the medium from 1 to 8 h of incubation, while cellular LH showed a corresponding decrease. GnRH (1nM) neither modified the uptake nor the incorporation of [3H]-glucosamine and [3H]-proline into total protein. The incorporation of [3H]-proline into cellular LH also was unaffected by GnRH. In contrast, GnRH stimulated a 3 to 4-fold increase in [3H]-glucosamine incorporation into cellular LH. The agonistic analogue, [des GlyNH210]-LHRH ethylamide, mimicked the GnRH effects and was 5 to 6 times more potent than GnRH. The antagonistic analogue, [D-Phe2, D-Phe6]-LHRH blocked the GnRH-stimulated effects. These results suggest that GnRH and agonistic analogues may preferentially regulate turnover or synthesis of the carbohydrate moiety of LH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22657/1/0000208.pd

Synthesis of Novel Azamacrocyclic Metal Ion Receptors Using a Modified Mannich Aminomethylation Reaction

A modified Mannich aminomethylation reaction was used to prepare a series of N-substituted-phenol-containing azacrown ether ligands. Ligands synthesized include aza-15-crown-5, aza-18-crown-6, azapyridino-18-crown-6, diaza-18-crown-6, diaza-21-crown-7 and diaza-24-crown-8 containing various substituted phenols, salicylaldehyde, and 5-chloro-8-hydroxyquinoline (CHQ) groups as side arms. The modified Mannich reaction was also used to prepare bi- and tricyclic azamacroheterocycles containing phenol units, benzoazacrown ethers, benzocryptands, and cryptohemispherands. The phenol- and CHQ-substituted azacrown ligands interact more strongly with metal ions than do the parent unsubstituted azacrown ethers. Bis-CHQ-substituted diaza-18-crown-6, wherein the CHQ groups are attached through their 7 positions, are particularly selective for K^+ over other alkali metal ions and for Ba^(2+) over all other metal ions studied

Synthesis of Novel Azamacrocyclic Metal Ion Receptors Using a Modified Mannich Aminomethylation Reaction

A modified Mannich aminomethylation reaction was used to prepare a series of N-substituted-phenol-containing azacrown ether ligands. Ligands synthesized include aza-15-crown-5, aza-18-crown-6, azapyridino-18-crown-6, diaza-18-crown-6, diaza-21-crown-7 and diaza-24-crown-8 containing various substituted phenols, salicylaldehyde, and 5-chloro-8-hydroxyquinoline (CHQ) groups as side arms. The modified Mannich reaction was also used to prepare bi- and tricyclic azamacroheterocycles containing phenol units, benzoazacrown ethers, benzocryptands, and cryptohemispherands. The phenol- and CHQ-substituted azacrown ligands interact more strongly with metal ions than do the parent unsubstituted azacrown ethers. Bis-CHQ-substituted diaza-18-crown-6, wherein the CHQ groups are attached through their 7 positions, are particularly selective for K^+ over other alkali metal ions and for Ba^(2+) over all other metal ions studied