From the Cutting Edge of Science: Last week in Science, Nature and PNAS

In the work "N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals", published in the latest issue of Science, a group of scientists from the California Institute of Technology in Pazenda, working under the leadership of Alexander Varshavsky, revealed the purpose of acetylation of N-terminal methionine – a very common modification of eukaryotic proteins (80% of all human proteins contain such a modification, in yeast – more than 50%), the function of which has remained unknown until now. Using saccharomyces yeast as a model organism, scientists have found that acetylation of methionine at the N-end of the protein can serve as a signal to degradation (the so–called degron) of the protein containing it for Doa10 - a protein involved in the mechanism of utilization of cellular proteins. Researchers have shown that Doa10 recognizes the same modification of some other amino acids: alanine, valine, serine, threonine and serine. After analyzing several yeast proteins that perform different functions in the cell, but contain one of the listed acetylated amino acids (called Ac-N-degrons) at the N-ends, the scientists came to the conclusion that these signals are prevalent among all signals of degradation of cellular proteins. Scientists note that more than 50% of yeast proteins and about 80% of human proteins contain Ac-N-degrons.

In the article "S-Nitrosylation from GSNOR Deficiency Impairs DNA Repair and Promotes Hepatocarcinogenesis", published in the latest issue of Science Translational Medicine, a group of scientists of Professor Limin Liu from the University of California at San Francisco with colleagues from the University of Texas Health Science Center in San Antonio found that insufficient production and the activity of the enzyme GSNOR (S-nitrosoglutathione reductase – S-nitroglutathione reductase) is one of the molecular factors contributing to the development of hepatocellular carcinoma, one of the most common malignant liver diseases. The researchers found that mice that did not produce the GSNOR protein were very sensitive to the spontaneous and carcinogen-induced occurrence of hepatocellular carcinoma, and in almost 50% of the examined people with this disease, the concentration of the GSNOR enzyme and its activity were significantly reduced. Apparently, the concentration of GSNOR and its activity can serve as biomarkers of the risk of developing hepatocellular carcinoma.

In the article "The landscape of somatic copy-number alteration across human cancers", published in the latest issue of Nature, a group of scientists from the Broad Institute Genome Research Center writes that the survival of malignant cells whose genomes contain many copies of sequences surrounding anti-apoptotic (preventing the implementation of the cell self-destruction program) MCL1 genes and BCL2L1, depends on the functioning of these genes. The researchers found that most sequences characterized by an altered number of copies in somatic cells – somatic copy-number alterations (SCNAs), and found in certain types of malignant tumors, were also detected in the chromosomes of cells of several other types of cancer.

In the article "Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence", published in the latest issue of PNAS, an international group of scientists working under the leadership of Chengjun Li from the University of Wisconsin-Madison warns about the possibility of highly pathogenic strains of influenza viruses – hybrids between currently circulating avian H5N1 and human H3N2 viruses. Lee's group evaluated the pathogenicity of potential recombinant viruses by creating all possible 254 hybrids between H5N1 and H3N2 strains and analyzing their pathogenicity in model animals. Of the 75 recombinant H5 viruses tested on mice, 22 turned out to be more pathogenic than H5N1, and three were extremely pathogenic, and the main role in increasing the pathogenicity of the H5N1 avian influenza virus was played by the appearance of the PB2 segment of the human H3N2 virus in its genome. Scientists are calling on the relevant regulatory authorities to monitor recombinant strains of the H5 avian influenza virus, paying special attention to the appearance of the PB2 segment of the human influenza virus in their genomes.

In the work "Specificity landscapes of DNA binding molecules elucidate biological function", published in the latest issue of PNAS, specialists from the University of Wisconsin-Madison propose an original methodology for assessing the specificity and strength of the interaction of a spectrum of DNA-binding molecules, including proteins and synthetic substances, with DNA fragments throughout the genome. To the surprise of scientists, the DNA-binding molecules they constructed turned out to be more specific than some similar natural proteins. The approach proposed by the researchers makes it possible to evaluate the effect of synthetic molecules on the regulation of gene activity in cultured cells, and also opens up prospects for the development of drugs that purposefully act on specific genome sequences.

Daria Chervyakova
Portal "Eternal youth" http://vechnayamolodost.ru based on Genomeweb materials24.02.2010