[The role of the proteasome for therapy of incurable diseases].
Proteins constitute the basic building elements of living organisms. Proteins have a limited lifetime in a cell. The so called "half-life period" of proteins is diverse and lasts from several minutes to several days. Regulatory proteins appear in a cell for a definite time and are short-lived. The proteins responsible for basic cell functions are stable and long-lived. Once their functions are fulfilled or because of their surfeit or damage, proteins are eliminated by degradation. Transformation processes of proteins are precisely controlled. There is also a strict association between protein metabolism and the energetic state of a cell. The main proteolytic cell systems are lysosomal and proteasome ones. The first (lysosomes) function in a simple and transparent way. The second system (proteasomes) is highly organized; by using ubiquitin it delivers "molecular label" and sends a marked protein for degradation. Efficient degradation of cellular proteins by the UPS route (ubiquitin - proteasome system) is essential for signal transduction, transcription adjustment, response to stress and control of receptors' activity. The dysfunction of the UPS route is crucial in the development of tumors, neurodegenerative diseases and diseases of immunological and infectious origin. Therefore, it is a challenge to elaborate methods of pharmacological intervention within this system involving, for example, the use of specific, low molecular-weight proteasome inhibitors and enzymes catalyzing the ubiquitination process. The article presents a review of advances in the field, including description of the lysosomal protein degradation route, proteasome model, and the phenomenon of protein aggregation. The summary of the experience on applied therapies, which use the processes of protein degradation as a basis, were also presented.
Bubko
Irena
I
Zakład Biochemii i Biofarmaceutyków, Narodowy Instytut Leków w Warszawie, 00-725 Warszawa. ibub@il.waw.pl
Gruber
Beata M
BM
Anuszewska
Elzbieta L
EL
D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D009369:Neoplasms / Q000628:therapy*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism* / Q000627:therapeutic use*; D025801:Ubiquitin / Q000378:metabolism*
D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex