L. important functions in the precise control of splicing factors trafficking within the nucleus. INTRODUCTION Proteasomes are large proteolytic complexes that play a central role in intracellular proteolysis and are particularly important for the tightly controlled degradation of many critical regulatory proteins (Ciechanover and Schwartz, 2004 ). The term proteasomes defines a family of complexes that share a common proteolytic core Rabbit polyclonal to IL24 (the 20S proteasome) but differ in the regulators associated with the complex (Demartino and Slaughter, 1993 ; Rechsteiner and Hill, 2005 ). This diversity of proteasome complexes might reflect the necessity for the cell to degrade hundreds of different proteins at the same time, often in a highly selective and regulated manner and in certain cases only at precise locations in the cell (Pines and Lindon, 2005 ). However, (R)-Simurosertib whether the activity of each of these complexes is restricted to a particular set of substrates or to particular cellular domains is presently unclear. The 20S proteasome is a cylindrical-shaped protein complex, comprising 28 subunits arranged in four stacked rings: two outer rings each made of seven alpha-type subunits (1C7) and two inner rings each made of seven beta-type subunits (1C7). The catalytic sites are enclosed in the inner catalytic chamber made by the -type subunits (Groll (R)-Simurosertib have suggested that it might be involved in cell cycle progression and have anti-apoptotic functions (Rechsteiner and Hill, 2005 ). However, its exact role in these processes is not understood. Biochemical analyses have shown that PA28 can activate peptide degradation by the 20S proteasome in vitro (Realini (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-07-0637) on February 6, 2008. REFERENCES Baldin V., Lukas J., Marcote M. J., Pagano M., Draetta G. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 1993;7:812C821. [PubMed] [Google Scholar]Barton L. F., Runnels H. A., Schell T. D., Cho Y., Gibbons R., Tevethia S. S., Deepe G. S., Jr, Monaco J. J. Immune defects in 28-kDa proteasome activator gamma-deficient mice. J. Immunol. 2004;172:3948C3954. [PubMed] [Google Scholar]Boireau S., et al. The transcriptional cycle of HIV-1 in real-time and live cells. J. Cell Biol. 2007;179:291C304. [PMC free article] [PubMed] [Google Scholar]Brooks P., Murray R. Z., Mason G. G., Hendil K. B., Rivett A. J. Association of immunoproteasomes with the endoplasmic reticulum. Biochem. J. 2000;352:611C615. [PMC free article] [PubMed] [Google Scholar]Caceres J. F., Misteli T., Screaton G. R., Spector D. L., Krainer A. R. Role of the modular domains of SR proteins in subnuclear localization and alternative splicing specificity. J. Cell Biol. 1997;138:225C238. [PMC free article] [PubMed] [Google Scholar]Cascio P., Call M., Petre B. M., Walz T., Goldberg A. L. Properties of the hybrid form of the 26S proteasome containing both 19S and PA28 complexes. EMBO J. 2002;21:2636C2645. [PMC (R)-Simurosertib free article] [PubMed] [Google Scholar]Chen M., Rockel T., Steinweger G., Hemmerich P., (R)-Simurosertib Risch J., Von Mikecz A. Subcellular recruitment of fibrillarin to nucleoplasmic proteasomes: implications for processing of a nucleolar autoantigen. Mol. Biol. Cell. 2002;13:3576C3587. [PMC free article] [PubMed] [Google Scholar]Chen X., Barton L. F., Chi Y., Clurman B. E., Roberts J. M. Ubiquitin-independent degradation of cell-cycle inhibitors by the REGgamma proteasome. Mol. Cell. 2007;26:843C852. [PMC free article] [PubMed] [Google Scholar]Ciechanover A., Schwartz A. L. The ubiquitin system: pathogenesis of human diseases and drug targeting. Biochim. Biophys. Acta. 2004;1695:3C17. [PubMed] [Google Scholar]Cioce M., Boulon S., Matera A. G., Lamond A. I. UV-induced fragmentation of Cajal bodies. J. Cell Biol. 2006;175:401C413. [PMC free article] [PubMed] [Google Scholar]Colwill K., Pawson T., Andrews B., Prasad J., Manley J. L., Bell J. C., Duncan P. I. The Clk/Sty protein kinase phosphorylates SR splicing factors and regulates their intranuclear distribution. (R)-Simurosertib EMBO J..