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The ubiquitin-proteasome system: A novel target for anticancer and anti-inflammatory drug research
Cellular & Molecular Biology Letters volume 13, pages 353–365 (2008)
Abstract
The ubiquitin-proteasome system is responsible for the degradation of most intracellular proteins, including those that control cell cycle progression, apoptosis, signal transduction and the NF-κB transcriptional pathway. Aberrations in the ubiquitin-proteasome system underlie the pathogenesis of many human diseases, so both the ubiquitin-conjugating system and the 20S proteasome are important targets for drug discovery. This article presents a few of the most important examples of the small molecule inhibitors and modulators targeting the ubiquitin-proteasome system, their mode of action, and their potential therapeutic relevance in the treatment of cancer and inflammatory-related diseases.
Abbreviations
- AML:
-
acute myeloid leukemia
- ARF:
-
acute renal failure
- BMSCs:
-
bone marrow stromal cells
- βTrPC:
-
β-transducin repeat containing protein
- CDK:
-
cyclindependent kinase
- ChT-L:
-
chymotrypsin-like
- C-L:
-
caspase-like
- CLL:
-
chronic lymphocytic leukemia
- DHT:
-
dihydroxytestosterone
- DOCA:
-
deoxycortycosterone
- DUB:
-
deubiquitinating enzyme
- E1:
-
ubiquitin-activating enzyme
- E2:
-
ubiquitin-conjugating enzyme
- E3:
-
ubiquitin-protein ligase
- ET-1:
-
endothelin-1
- Hdm2:
-
human counterpart of Mdm2
- HIF-1:
-
hypoxia inducible factor
- IKK:
-
IκB kinase
- IL-1:
-
interleukin
- INF-γ:
-
interferon gamma
- LMP:
-
low-molecular-mass polypeptide
- Mdm2:
-
murine double minute 2
- Met-AP-2:
-
metionine aminopeptidase-2
- MHC:
-
major histocompatibility complex
- MM:
-
multiple myeloma
- NF-κB:
-
nuclear factor-kappaB
- pIκBα:
-
phosphorylated inhibitor-κβ
- Protacs:
-
proteolytic targeting chimeric molecules
- pVHL:
-
phosphorylated von Hippel-Lindau tumor suppressor
- RITA:
-
reactivation of p53 and induction of tumor cell apoptosis
- SCF:
-
complex formed by Skp1, cullin and F-box protein
- siRNA:
-
small interfering RNA
- SKP2:
-
S-phase kinase associated protein 2
- SMPI:
-
small molecule proteolysis inducers
- T-L:
-
trypsin-like
- TNF:
-
tumor necrosis factor
- UPS:
-
ubiquitin-proteasome system
- VCAM:
-
various leukocyte adhesion molecules
- VEGF:
-
vascular endothelial growth factor
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Paper authored by participants of the international conference: XXXIV Winter School of the Faculty of Biochemistry, Biophysics and Biotechnology of Jagiellonian University, Zakopane, March 7–11, 2007, “The Cell and Its Environment”. Publication cost was partially covered by the organisers of this meeting.
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Ostrowska, H. The ubiquitin-proteasome system: A novel target for anticancer and anti-inflammatory drug research. Cell Mol Biol Lett 13, 353–365 (2008). https://doi.org/10.2478/s11658-008-0008-7
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DOI: https://doi.org/10.2478/s11658-008-0008-7