Vnitr Lek 2006, 52(4):371-378

Ubiquitins, proteasomes, sumoylation and application today and in future for cancer and other diseases therapy I. Ubiquitin-proteasome system and the transcription factor NF-κB

O. Fuchs^1,*, R. Neuwirtová²

¹ Ústav hematologie a krevní transfuze, Praha, ředitel prof. MUDr. Pavel Klener, DrSc.

² I. interní klinika 1. lékařské fakulty UK a VFN, Praha, přednosta prof. MUDr. Pavel Klener, DrSc.

Proteasome is protein complex with proteolytic activity. Proteasomes are in addition to lysosomes the main proteolytic machinery of the eukaryotic cell. Proteins destined for degradation in proteasomes are marked by ubiquitinylation, which consists in attachment of polyubiquitin to relevant protein. The transport of polyubiquitinylated protein follows to proteasome, where protein is cleaved into small peptides. Besides polyubiquitin attachment to protein, monoubiquitinylation of proteins exists and has an important role in DNA repair, transcription of genes, endocytosis and signal transduction. The function of an important transcription factor NF-κB is connected with proteasome. NF-κB is activated after the proteolysis of its inhibitor IκB in proteasome. Ubiqutinylation and degradation of protein in proteasome and the activation of NF-κB play significant roles in taking proteins away and in expression of great numbers of genes important for the regulation of the cell cycle and apoptosis of cells. The inhibition of proteasomes has antiproliferative and antiinflammatory effects and opens new therapeutic approaches to a treatment of cancer and some inflammatory diseases. We divided the review into three parts: I. Ubiquitin-proteasome system and the transcription factor NF-κB, II. Sumoylation and neddylation as post-translational modification of proteins similar to ubiquitinylation and their significance and lastly III. Using of the knowledge of ubiquitin-proteasome system in cancer and other diseases therapy.

Keywords: ubiquitin; proteasome; transcription factor NF-κB

Received: October 7, 2005; Accepted: January 26, 2006; Published: April 1, 2006  Show citation