Public Release:  News tips from the Journal of Biological Chemistry

American Society for Biochemistry and Molecular Biology

Articles to be published in the April 20, 2007 issue of the Journal of Biological Chemistry (Vol. 282, No. 16)

ARTICLE HIGHLIGHTS

  • Sperm Activates Egg with New Protein
  • New Chemical Effective against Anthrax
  • New Protein Controls Growth of Hepatitis C Virus
  • Repressing Genes
  • Potential New Drug against African Sleeping Sickness


Sperm Activates Egg with New Protein

This article was featured as a "Paper of the Week" by the Journal of Biological Chemistry's Editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.

Researchers have discovered a new protein involved in the fertilization of an egg by sperm, providing useful information for scientists developing reproductive technologies and for better understanding reproductive disorders.

When the membranes of the sperm head and egg start fusing and create an opening between them, the sperm cell releases proteins through the opening that activate the egg. This allows the sperm cell to further enter the egg and mix its material with that of the egg, thus creating one cell - the zygote. The egg activation steps are well known, but it is not yet clear which molecules initiate the activation process.

Richard Oko and colleagues report a new protein that appears to play a key role in the first stages of egg activation. They isolated the protein, called postacrosomal sheath WW domain-binding protein (PAWP), from several animal species and investigated its role in fertilization. They blocked PAWP from functioning in sperm cells and then injected them in eggs with a common in vitro fertilization technique called intracytoplasmic sperm injection. Without PAWP, the sperm cells were unable to activate the eggs, confirming the protein's role in initiating the activation process. The scientists also located PAWP to the region of the sperm cell's head already known to be involved in egg activation.

Article: "PAWP, a Sperm-specific WW Domain-binding Protein, Promotes Meiotic Resumption and Pronuclear Development during Fertilization" by Alexander T. H. Wu, Peter Sutovsky, Gaurishankar Manandhar, Wei Xu, Mika Katayama, Billy N. Day, Kwang-Wook Park, Young-Joo Yi, Yan Wei Xi, Randall S. Prather, and Richard Oko

MEDIA CONTACT: Richard Oko, Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada; tel: 613-533-2858; e-mail: ro3@post.queensu.ca


New Chemical Effective against Anthrax

Scientists have identified a chemical that could be used as a new drug against anthrax.

Anthrax is a deadly disease caused by spores that germinate into bacteria, which then release a deadly toxin. Spores that are inhaled by animals or people germinate in the lungs to form bacteria, which then spread throughout the body, releasing the toxin and triggering the disease. Since spore germination is needed to cause infection, preventing germination is a potentially efficient way to stop the infection.

Jurgen Brojatsch, Ernesto Abel-Santos, and colleagues identified seven chemicals that block the germination of cultured anthrax spores. They also showed that one of these compounds, 6-thioguanosine, blocked the spores' germination inside mammalian cells, thus blocking anthrax infection. The scientists are now planning to test 6-thioguanosine in mice infected with the anthrax bacterium. This compound is a known anticancer agent with well-studied pharmacological properties, which could help save time and money if it is used in clinical trials.

Article: "Identification of an in Vivo Inhibitor of Bacillus anthracis Spore Germination" by Monique Akoachere, Raynal C. Squires, Adel M. Nour, Ludmyl Angelov, Jurgen Brojatsch, and Ernesto Abel-Santos

MEDIA CONTACT: Jurgen Brojatsch, Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York; tel.: 718-430-3079; e-mail: brojatsc@aecom.yu.edu

MEDIA CONTACT: Ernesto Abel-Santos, Department of Chemistry, University of Nevada-Las Vegas, Las Vegas, Nev.; tel: 702-895-2608; e-mail: ernesto.abelsantos@unlv.edu


New Protein Controls Growth of Hepatitis C Virus

Researchers reveal a new protein that prevents the hepatitis C virus from replicating, which could help devise new drugs against hepatitis C.

Hepatitis C is a blood-borne, infectious disease that can cause liver inflammation, fibrotic scarring of the liver - or cirrhosis - and liver cancer. The virus spreads within its host by replicating its RNA and using it to build proteins that form new viruses and by inhibiting various antiviral proteins inside host cells. By understanding both mechanisms, scientists hope to prevent the virus from replicating, thus stopping the infection.

Stanley M. Lemon and colleagues discovered a new protein involved in stopping the virus from replicating. Called p21-activated kinase 1, the protein is known to play a role in several cellular signaling pathways, but it has not been shown previously to be involved in regulating the replication of hepatitis C virus.

Article: "p21-activated Kinase 1 Is Activated through the Mammalian Target of Rapamycin/p70 S6 Kinase Pathway and Regulates the Replication of Hepatitis C Virus in Human Hepatoma Cells" by Hisashi Ishida, Kui Li, MinKyung Yi, and Stanley M. Lemon

MEDIA CONTACT: Stanley M. Lemon, Center for Hepatitis Research, University of Texas Medical Branch, Galveston; tel: 409-747-7048; e-mail: smlemon@utmb.edu


Repressing Genes

Researchers report that most genes are repressed through a mechanism by which methyl molecules are attached to DNA.

The cells of a given tissue can express only certain genes while others are silenced. This process, called gene repression, allows cells to perform specialized tasks that are different among various organs. Previous studies have shown that genes are repressed when methyl molecules are attached to them - a process called methylation - but such studies have not shown that all genes are repressed exclusively by this modification.

Howard Cedar and colleagues show that methylation is the main gene repression mechanism, but other mechanisms - such as the modification of chromosome proteins called histones and delays in DNA replication - play an important role as well.

Article: "Role of DNA Methylation in Stable Gene Repression" by Laura Lande-Diner, Jianmin Zhang, Ittai Ben-Porath, Ninette Amariglio, Ilana Keshet, Merav Hecht, Veronique Azuara, Amanda G. Fisher, Gideon Rechavi, and Howard Cedar

MEDIA CONTACT: Howard Cedar, Department of Cellular Biochemistry and Human Genetics, Hebrew University Medical School, Jerusalem, Israel; tel.: 972-2-675-8167; e-mail: cedar@md.huji.ac.il


Potential New Drug against African Sleeping Sickness

Researchers have shown that a drug that was extensively tested against cancer may also qualify as a new drug against African sleeping sickness.

African sleeping sickness, a disease marked by fever, headaches, and sleepiness, is caused by a parasite that is transmitted to humans through tsetse fly bites. The parasite escapes destruction by the host immune system because it is surrounded with a "coat" made of proteins that constantly change. But the parasite may have a weakness: It contains very low amounts of cytidine triphosphate (CTP), a molecule essential for cell survival.

Artur Fijolek and colleagues showed that a protein called cytidine triphosphate synthetase, which helps synthesize CTP, was inhibited by acivicin, an anticancer drug previously tested in humans and animals but now abandoned. The scientists tested the action of the drug on mice infected with the trypanosome parasite and showed that the infection was suppressed for at least one month without serious side effects, raising hopes that acivicin could be used as a drug against African sleeping sickness.

Article: "Expression, Purification, Characterization, and in Vivo Targeting of Trypanosome CTP Synthetase for Treatment of African Sleeping Sickness" by Artur Fijolek, Anders Hofer, and Lars Thelander

MEDIA CONTACT: Artur Fijolek, Department of Medical Biochemistry and Biophysics, Umea University, SE-901 87 Umea, Sweden; tel: +46-90-786-5263; e-mail: artur.fijolek@medchem.umu.se

###

The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society's student members attend undergraduate or graduate institutions.

Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.

For more information about ASBMB, see the Society's Web site at www.asbmb.org

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.