The Conserved Domain CR2 of Epstein–Barr Virus Nuclear Antigen Leader Protein Is Responsible Not Only for Nuclear Matrix Association but Also for Nuclear Localization

AbstractThere is a growing body of evidence for the importance of the nuclear matrix in various nuclear events including gene expression and DNA replication. Epstein–Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) is a nuclear matrix-associated protein that has been suggested to play an important role in EBV-induced transformation. To define the biological significance of the association of EBNA-LP with the nuclear matrix, we mapped the domain of EBNA-LP responsible for nuclear matrix association and investigated the functions of the EBNA-LP mutant mutagenized by substitution of alanines for the cluster of arginine residues in the mapped region. The results of the present study were as follows. (i) Transiently expressed EBNA-LP in COS-7 or BOSC23 cells was associated with the nuclear matrix, similarly to that in EBV-infected B cells. (ii) Mutational analysis of EBNA-LP revealed that a 10-amino acid segment of EBNA-LP is critical for nuclear matrix association of the protein. Interestingly, the identified region overlapped with the region CR2 of EBNA-LP conserved among a subset of primate gammaherpesviruses. The identified segment is referred to as EBNA-LP NMTS (nuclear matrix targeting signal). (iii) The EBNA-LP mutant with the arginine to alanine substitutions in NMTS was no longer localized not only to the nuclear matrix but also to the nucleus. (iv) The EBNA-LP mutant lacked its ability to coactivate EBNA-2-dependent transactivation. These results indicated that EBNA-LP needs to be localized in the nucleus and/or associated with the nuclear matrix through CR2 to elicit its function such as the coactivation of the EBNA-2-dependent transcriptional activation

Valse con sordino

score and part. 31 cm

Aus der Geigenwelt: Eine Sammlung von 20 Stücken für Violine und Klavier zusammengestellt, revidiert und bezeichnet von Professor Issay Barmas.

score (3 v. in 1) and part. 34 cm

Preludes, piano, op. 1

Cover-title in Russian and German. --- Illuminated cover-title. --- Each part has separate t.-p

Deux poèmes pour piano, par I. Dobroven. Op. 3.

2 v. in 1. 35 cm. 1. Es-moll. 2. Gis-moll

Preludes, piano, op. 1

Cover-title in Russian and German. --- Illuminated cover-title. --- Each part has separate t.-p

Issay Barmas : Violin Virtuose, Lehrer für die Violin-Ausbildungsklassen am Stern'schen Konservatorium.

Short biographical article on Barmas, with emphasis on his activities in Berlin.TroszeniumViolin teacher at Stern Conservatory, Berlin. Born 1872 in Odessa (Russia). Died in 1946.Processed for digitizationProcessed for digitizationRedesignated as manuscriptSent for digitizationReturned from digitizationLinked to online manifestationdigitize

Functional analysis of PprI in the DNA damage response mechanism of Deinococcus radiodurans

Analysis of the genome sequences of Deinococcus spp. discovered the radiation/desiccation response (RDR) motif, existing upstream of the radiation-inducible genes (RDR regulons) such as pprA and recA genes. The RDR motif serves as an operator sequence in the unique DNA repair response system. Another regulatory protein DdrO binds RDR motif. Following DNA damage, the metalloprotease activity of PprI cleaves DdrO, resulting in induction of the RDR regulon. However, the detailed functional site of PprI protein in the DNA damage response mechanism is poorly understood. In an effort to gain an insight into the role of the PprI in DNA damage response mechanism in D. radiodurans, firstly, we generated a pprI-deleted mutant strain and pprI expression plasmid. Consequently, we successfully generated complete deletion strains for the D. radiodurans pprI genes. This deletion strain SXPI carrying pRAD1 exhibited extreme sensitivity to gamma-rays compare to the wild type strain carrying pRAD1. In the strain SXPI carrying pEXpprI, the survival rate following treatment with gamma rays was restored to the similar level of that in the wild type. This result suggests that D. radiodurans PprI is a key protein for the repair of damage induced by gamma rays as shown in the previous study

MLL fusion proteins link transcriptional coactivators to previously active CpG-rich promoters.

Mixed-lineage leukemia (MLL) maintains the expression of cellular memory genes during development, while leukemic MLL fusion proteins aberrantly maintain expression of hematopoietic stem cell program genes such as HOXA9 to cause leukemia. However, the molecular mechanism of gene activation is unclear. Here we show that only two functional modules are necessary and sufficient for target recognition: those that bind to non-methylated CpGs and di-/tri-methylated histone H3 lysine 36 (H3K36me2/3). An artificial protein composed of the two targeting modules and an interaction domain for AF4-family coactivators can functionally substitute for MLL fusion proteins. Because H3K36me2/3 markers are indicative of active transcription, MLL fusion proteins target previously active CpG-rich genes and activate transcription by recruiting coactivators thereto. Our results indicate that such chromatin context-dependent gene activation is the fundamental mechanism by which MLL fusion proteins maintain the expression of the cellular memory/hematopoietic stem cell program genes