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The Ubiquitin-Proteasome Pathway and Epigenetic Modifications in Cancer       
Yazarlar (4)
Azmi Yerlikaya
Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Dr. Öğr. Üyesi Ertan KANBUR Dr. Öğr. Üyesi Ertan KANBUR
Kırşehir Ahi Evran Üniversitesi, Türkiye
Bruce A Stanley
Emrah Tümer
Türkiye
Devamını Göster
Özet
Background: The ubiquitin-proteasome pathway is involved in almost all cellular processes (cell cycle, gene transcription and translation, cell survival and apoptosis, cell metabolism and protein quality control) mainly through the specific degradation of the majority of intracellular proteins (>80%) or partial processing of transcription factors (e.g., NF-kappa B). A growing amount of evidence now indicates that epigenetic changes are also regulated by the ubiquitin-proteasome pathway. Recent studies indicate that epigenetic regulations are equally crucial for almost all biological processes as well as for pathological conditions such as tumorigenesis, as compared to non-epigenetic control mechanisms (i.e., genetic alterations or classical signal transduction pathways).
Objective: Here, we reviewed the recent work highlighting the interaction of the ubiquitin-proteasome pathway components (e.g., ubiquitin, E1, E2 and E3 enzymes and 26S proteasome) with epigenetic regulators (histone deacetylases, histone acetyltransferases and DNA methyltransferases).
Results: Alterations in the regulation of the ubiquitin-proteasome pathway have been discovered in many pathological conditions. For example, a 2- to 32-fold increase in proteasomal activity and/or subunits has been noted in primary breast cancer cells. Although proteasome inhibitors have been successfully applied in the treatment of hematological malignancies (e.g., multiple myeloma), the clinical efficacy of the proteasomal inhibition is limited in solid cancers. Interestingly, recent studies show that the ubiquitin-proteasome and epigenetic pathways intersect in a number of ways through the regulation of epigenetic marks (i.e., acetylation, methylation and ubiquitylation).
Conclusion: It is therefore believed that novel treatment strategies involving new generation ubiquitin-proteasome pathway inhibitors combined with DNA methyltransferase, histone deacetylase or histone acetyltransferase inhibitors may produce more effective results with fewer adverse effects in cancer treatment as compared to standard chemotherapeutics in hematological as well as solid cancers.
Anahtar Kelimeler
Bortezomib | cancer | epigenetics | histone deacetylase | proteasome | ubiquitin
Makale Türü Diğer (Teknik, not, yorum, vaka takdimi, editöre mektup, özet, kitap krıtiği, araştırma notu, bilirkişi raporu ve benzeri)
Makale Alt Türü SCI, SSCI, AHCI, SCI-Exp dergilerinde yayımlanan teknik not, editöre mektup, tartışma, vaka takdimi ve özet türünden makale
Dergi Adı ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
Dergi ISSN 1871-5206 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Makale Dili Türkçe
Basım Tarihi 01-2021
Cilt No 21
Sayı 1
Sayfalar 20 / 32
Doi Numarası 10.2174/1871520620666200811114159
Makale Linki http://dx.doi.org/10.2174/1871520620666200811114159
BM Sürdürülebilir Kalkınma Amaçları
Atıf Sayıları
WoS 13
Google Scholar 17
The Ubiquitin-Proteasome Pathway and Epigenetic Modifications in Cancer

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