the gag cleavage product, p12, is a functional constituent of the murine leukemia virus pre-integration complex呕吐乳沟产品,p12,小鼠白血病病毒整合前的功能成分复杂.pdf

The Gag Cleavage Product, p12, is a Functional Constituent of the Murine Leukemia Virus Pre- Integration Complex 1. 1. 1 2 1 1 Adi Prizan-Ravid , Efrat Elis , Nihay Laham-Karam , Sara Selig , Marcelo Ehrlich , Eran Bacharach * 1 Department of Cell Research and Immunology, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel, 2 Molecular Medicine Laboratory, Rambam Health Campus and Rappaport Faculty of Medicine, Technion, Haifa, Israel Abstract The p12 protein is a cleavage product of the Gag precursor of the murine leukemia virus (MLV). Specific mutations in p12 have been described that affect early stages of infection, rendering the virus replication-defective. Such mutants showed normal generation of genomic DNA but no formation of circular forms, which are markers of nuclear entry by the viral DNA. This suggested that p12 may function in early stages of infection but the precise mechanism of p12 action is not known. To address the function and follow the intracellular localization of the wt p12 protein, we generated tagged p12 proteins in the context of a replication-competent virus, which allowed for the detection of p12 at early stages of infection by immunofluorescence. p12 was found to be distributed to discrete puncta, indicative of macromolecular complexes. These complexes were localized to the cytoplasm early after infection, and thereafter accumulated adjacent to mitotic chromosomes. This chromosomal accumulation was impaired for p12 proteins with a mutation that rendered the virus integration-defective. Immunofluorescence