The proteasome in cancer biology and treatment

Citation
F. Pajonk et Wh. Mcbride, The proteasome in cancer biology and treatment, RADIAT RES, 156(5), 2001, pp. 447-459
Citations number
180
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Experimental Biology
Journal title
RADIATION RESEARCH
ISSN journal
0033-7587 → ACNP
Volume
156
Issue
5
Year of publication
2001
Part
1
Pages
447 - 459
Database
ISI
SICI code
0033-7587(200111)156:5<447:TPICBA>2.0.ZU;2-3
Abstract
During the last 30 years, investigation of the transcriptional and translat ional mechanisms of gene regulation has been a major focus of molecular can cer biology. More recently, it has become evident that cancer-related mutat ions and cancer-related therapies also can affect post-translational proces sing of cellular proteins and that control exerted at this level can be cri tical in defining both the cancer phenotype and the response to therapeutic intervention. One post-translational mechanism that is receiving considera ble attention is degradation of intracellular proteins through the multicat alytic 26S proteasome. This follows growing recognition of the fact that pr otein degradation is a well-regulated and selective process that can differ entially control intracellular protein expression levels. The proteasome is responsible for the degradation of all short-lived proteins and 70-90% of all long-lived proteins, thereby regulating signal transduction through pat hways involving factors such as AP1 and NFKB, and processes such as cell cy cle progression and arrest, DNA transcription, DNA repair/misrepair, angiog enesis, apoptosis/survival, growth and development, and inflammation and im munity, as well as muscle wasting (e.g. in cachexia and sepsis). In this re view, we discuss the potential involvement of the proteasome in both cancer biology and cancer treatment. (C) 2001 by Radiation Research Society.