Pharmacological Modulation of Ubiquitin-Proteasome Pathways in Oncogenic Signaling.
Anmol Sharma,Heena Khan,Thakur Gurjeet Singh,Amarjot Kaur Grewal,Agnieszka Najda,Małgorzata Kawecka-Radomska,Mohamed Kamel,Ahmed E. Altyar,Mohamed M. del-Daim +8 more
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TLDR
A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on modulation of ubiquitin-proteasome pathways in oncogenic signaling as discussed by the authors.Abstract:
The ubiquitin-proteasome pathway (UPP) is involved in regulating several biological functions, including cell cycle control, apoptosis, DNA damage response, and apoptosis. It is widely known for its role in degrading abnormal protein substrates and maintaining physiological body functions via ubiquitinating enzymes (E1, E2, E3) and the proteasome. Therefore, aberrant expression in these enzymes results in an altered biological process, including transduction signaling for cell death and survival, resulting in cancer. In this review, an overview of profuse enzymes involved as a pro-oncogenic or progressive growth factor in tumors with their downstream signaling pathways has been discussed. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elsevier) databases was carried out to understand the nature of the extensive work done on modulation of ubiquitin-proteasome pathways in oncogenic signaling. Various in vitro, in vivo studies demonstrating the involvement of ubiquitin-proteasome systems in varied types of cancers and the downstream signaling pathways involved are also discussed in the current review. Several inhibitors of E1, E2, E3, deubiquitinase enzymes and proteasome have been applied for treating cancer. Some of these drugs have exhibited successful outcomes in in vivo studies on different cancer types, so clinical trials are going on for these inhibitors. This review mainly focuses on certain ubiquitin-proteasome enzymes involved in developing cancers and certain enzymes that can be targeted to treat cancer.read more
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References
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TL;DR: DUBs are subject to multiple layers of regulation that modulate both their activity and their specificity, and due to their wide-ranging involvement in key regulatory processes, these enzymes might provide new therapeutic targets.
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TL;DR: An inventory of the deubiquitinating enzymes encoded in the human genome is presented and the literature concerning these enzymes is reviewed, with particular emphasis on their function, specificity, and the regulation of their activity.
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Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome
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Identification of a Primary Target of Thalidomide Teratogenicity
Takumi Ito,Hideki Ando,Takayuki Suzuki,Toshihiko Ogura,Kentaro Hotta,Yoshimasa Imamura,Yuki Yamaguchi,Hiroshi Handa +7 more
TL;DR: A basis for thalidomide teratogenicity is revealed and may contribute to the development of new thalidmide derivatives without teratogenic activity.
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The proteasome - paradigm of a self-compartmentalizing protease
TL;DR: The work of one of us (W. B.) was supported by a grant of the Human Frontiers Science Program and the wish to thank Drs.