Nuclear proteasomes play a role in organization of the cell nucleus and in disease

On Thursday September 15th, 2005 at 5:15 pm, PD Dr. Anna von Mikecz will be our guest HPI-seminar speaker. Dr. von Mikecz, currently head of a research group at the Institut für Umweltmedizinische Forschung at University of Düsseldorf, is an expert on the cell biology of nuclear proteins and on autoimmunity. Her recent research is focussed on the nuclear ubiquitin proteasome system (nUPS) and its role in nuclear structure and function.

It has been well established over the last decades that proteasomes occur both in the cytoplasm and in the nucleus. In contrast to many rather well studied aspects of protease mediated degradation of proteins in the cytoplasm, there is currently scarce information on the localization and role of proteasomes in the nucleus for nuclear protein degradation. In her presentation she will present the recent progress she has made on the localization, dynamics and activity of proteasomes in specific subnuclear domains. The exciting information she gained has important implications for understanding of the architecture and functions of the nucleus.
She has also developed recently a fascinating new system for induction of aberrant protein clusters in the nucleus and will present data on its relevance for studies on cell cycle arrest, senescence and subnuclear pathology. Recently Dr. Mikecz has introduced a model on xenobiotic-induced autoimmunity and protein aggregation diseases, which share common subnulcear pathology, and suggests the possibility that these diseases are linked by common molecular mechanisms through nUPS (see figure for integrated view on nUPS functions). Increasing evidence suggests that nUPS can affect the expression levels and subcellular localization of transcription factors, oncogenic and viral proteins, proteins involved in stress and DNA repair and further indicates the relevance of this research for all major disciplines of life sciences including virology, tumor biology and neurology.

For additional information on Dr. Mickecz´s research work on this subject please refer to her three most recent publications from the references provided:

• Chen M, von Mikecz A. (2005) Xenobiotic-induced recruitment of autoantigens to nuclear proteasomes suggests a role for altered antigen processing in scleroderma. Ann N Y Acad Sci.1051:382-9.
• von Mikecz A. (2005) Xenobiotic-induced autoimmunity and protein aggregation diseases share a common subnuclear pathology. Autoimmun Rev. Apr;4(4):214-8.
• Chen M, von Mikecz A. (2005) Proteasomal processing of nuclear autoantigens in systemic autoimmunity. Autoimmun Rev. 4(3):117-22.