Proteasomes degrade proteins in focal subdomains of the human cell nucleus
Author:
Rockel Thomas Dino1, Stuhlmann Dominik2, von Mikecz Anna1
Affiliation:
1. Institut für umweltmedizinische Forschung at Heinrich-Heine-University, Auf'm Hennekamp 50, 40225 Düsseldorf, Germany 2. Institute for Biochemistry and Molecular Biology I, Heinrich-Heine-University, 40225 Düsseldorf, Germany
Abstract
The ubiquitin proteasome system plays a fundamental role in the regulation of cellular processes by degradation of endogenous proteins. Proteasomes are localized in both, the cytoplasm and the cell nucleus, however, little is known about nuclear proteolysis. Here, fluorogenic precursor substrates enabled detection of proteasomal activity in nucleoplasmic cell fractions (turnover 0.0541 μM/minute) and nuclei of living cells (turnover 0.0472 μM/minute). By contrast, cell fractions of nucleoli or nuclear envelopes did not contain proteasomal activity. Microinjection of ectopic fluorogenic protein DQ-ovalbumin revealed that proteasomal protein degradation occurs in distinct nucleoplasmic foci, which partially overlap with signature proteins of subnuclear domains, such as splicing speckles or promyelocytic leukemia bodies, ubiquitin, nucleoplasmic proteasomes and RNA polymerase II. Our results establish proteasomal proteolysis as an intrinsic function of the cell nucleus.
Publisher
The Company of Biologists
Reference56 articles.
1. Andersen, J. S., Lyon, C. E., Fox, A. H., Leung, A. K., Lam, Y. W., Steen, H., Mann, M. and Lamond, A. I. (2002). Directed proteomic analysis of the human nucleolus. Curr. Biol.12, 1-11. 2. Anton, L. C., Schubert, U., Bacik, I., Princiotta, M. F., Wearsch, P. A., Gibbs, J., Day, P. M., Realini, C., Rechsteiner, M. C., Bennink, J. R.et al. (1999). Intracellular localization of proteasomal degradation of a viral antigen. J. Cell Biol.146, 113-124. 3. Arabi, A., Rustum, C., Hallberg, E. and Wright, A. P. H. (2003). Accumulation of c-Myc and proteasomes at the nucleoli of cells containing elevated c-Myc protein levels. J. Cell Sci.116, 1707-1717. 4. Baumeister, W., Walz, J., Zuhl, F. and Seemuller, E. (1998). The proteasome: paradigm of a self-compartmentalizing protease. Cell92, 367-380. 5. Berneburg, M., Grether-Beck, S., Kurten, V., Ruzicka, T., Briviba, K., Sies, H. and Krutmann, J. (1999). Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion. J. Biol. Chem.274, 15345-15349.
Cited by
88 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|