Tip60 acetyltransferase activity is controlled by phosphorylation

Here we show that the phosphorylation of histone acetyltransferase Tip60, a target of human immunodeficiency virus, type 1-encoded transactivator Tat, plays a crucial role in the control of its catalytic activity. Baculovirus-based expression and purification of Tip60 combined with mass spectrometry allowed the identification of serines 86 and 90 as two major sites of phosphorylation in vivo. The phosphorylation of Tip60 was found to modulate its histone acetyltransferase activity. One of the identified phosphorylated serines, Ser-90, was within a consensus cyclin B/Cdc2 site. Ser-90 was specifically phosphorylated in vitro by the cyclin B/Cdc2 complex. Accordingly, the phosphorylation of Tip60 was enhanced after drug-induced arrest of cells in G(2)/M. This G(2)/M-dependent phosphorylation of Tip60 was abolished by treating cells with a specific inhibitor of the cyclin-dependent kinase, roscovitin. All together, these results strongly suggest a G(2)/M-dependent control of Tip60 activity.     

Isolation of an adhesin from Staphylococcus aureus that binds Lewis blood group antigen and its relevance to sudden infant death syndrome

Abstract A 67 kDa protein was isolated from cell membrane preparations of Staphylococcus aureus (NCTC 10655) by affinity adsorption with synthetic Lewis antigen conjugated to Synsorb beads. Pre-treatment of buccal epithelial cells expressing Lewis with the purified protein reduced binding of the staphylococcal strain to a greater extent than the material not bound to the Synsorb beads. The significance of this work is discussed with reference to expression of Lewis antigen in infants and the proposed role of toxigenic strains of staphylococci in some cases of sudden infant death syndrome.     

Rodent leptospirosis in Colorado

A study was conducted to evaluate leptospirosis in brown rats (Rattus norvegicus), muskrats (Ondatra zibethicus) and mice (Mus musculus) in southeastern Larimer County, Colorado. Leptospira serotype icterohaemorrhagiae was isolated from fourteen of 143 feral brown rats, an infection rate of 9.8%. Serological evidence of infection with this stereotype was found in 66.4% of the rats. Serological evidence of L. serotype ballum infection was present in three of 17 muskrats. Leptospires were seen in histological sections of kidney tissue from two of 61 feral mice. No isolations were made from cultures and serology was not done on mice.     

Various Polar Tripeptides as Asymmetric Organocatalyst in Direct Aldol Reactions in Aqueous Media

A series of tripeptide organocatalysts containing a secondary amine group and two amino acids with polar side chain units were developed and evaluated in the direct asymmetric intermolecular aldol reaction of 4‐nitrobenzaldehyde and cyclohexanone. The effectiveness of short polar peptides as asymmetric catalysts in aldol reactions to attain high yields of enantio‐ and diastereoselective isomers were investigated. In a comparison, glutamic acid and histidine produced higher % ee and yields when they were applied as the second amino acid in short trimeric peptides. These short polar peptides were found to be efficient organocatalysts for the asymmetric aldol addition reaction in aqueous media. Chirality 25:726–734, 2013. © 2013 Wiley Periodicals, Inc     

miR-143 expression profiles in urinary bladder cancer: correlation with clinical and epidemiological parameters

Molecular Biology Reports - Hsa-mir-143 and hsa-let-7c have been reported to be deregulated in multiple neoplasms. The main purpose of this study was to investigate the expression of these miRNAs...     

Acetylation and phosphorylation of SRSF2 control cell fate decision in response to cisplatin

SRSF2 is a serine/arginine-rich protein belonging to the family of SR proteins that are crucial regulators of constitutive and alternative pre-mRNA splicing. Although it is well known that phosphorylation inside RS domain controls activity of SR proteins, other post-translational modifications regulating SRSF2 functions have not been described to date. In this study, we provide the first evidence that the acetyltransferase Tip60 acetylates SRSF2 on its lysine 52 residue inside the RNA recognition motif, and promotes its proteasomal degradation. We also demonstrate that the deacetylase HDAC6 counters this acetylation and acts as a positive regulator of SRSF2 protein level. In addition, we show that Tip60 downregulates SRSF2 phosphorylation by inhibiting the nuclear translocation of both SRPK1 and SRPK2 kinases. Finally, we demonstrate that this acetylation/phosphorylation signalling network controls SRSF2 accumulation as well as caspase-8 pre-mRNA splicing in response to cisplatin and determines whether cells undergo apoptosis or G(2)/M cell cycle arrest. Taken together, these results unravel lysine acetylation as a crucial post-translational modification regulating SRSF2 protein level and activity in response to genotoxic stress.