The role of ubiquitination in tumorigenesis and targeted drug discovery

Signal Transduction and Targeted Therapy
Lu DengPing Wang

Abstract

Ubiquitination, an important type of protein posttranslational modification (PTM), plays a crucial role in controlling substrate degradation and subsequently mediates the "quantity" and "quality" of various proteins, serving to ensure cell homeostasis and guarantee life activities. The regulation of ubiquitination is multifaceted and works not only at the transcriptional and posttranslational levels (phosphorylation, acetylation, methylation, etc.) but also at the protein level (activators or repressors). When regulatory mechanisms are aberrant, the altered biological processes may subsequently induce serious human diseases, especially various types of cancer. In tumorigenesis, the altered biological processes involve tumor metabolism, the immunological tumor microenvironment (TME), cancer stem cell (CSC) stemness and so on. With regard to tumor metabolism, the ubiquitination of some key proteins such as RagA, mTOR, PTEN, AKT, c-Myc and P53 significantly regulates the activity of the mTORC1, AMPK and PTEN-AKT signaling pathways. In addition, ubiquitination in the TLR, RLR and STING-dependent signaling pathways also modulates the TME. Moreover, the ubiquitination of core stem cell regulator triplets (Nanog, Oct4 and Sox2) and me...Continue Reading

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Oct 3, 2020·Molecular Cancer·Tianshui SunQing Yang
Jun 4, 2020·International Journal of Molecular Sciences·Hong-Beom ParkKwang-Hyun Baek
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Jan 14, 2021·Signal Transduction and Targeted Therapy·Xiaofei Zhou, Shao-Cong Sun
Jan 5, 2021·Biotechnology and Applied Biochemistry·Zhengxin WuXuehui Hong
Jan 23, 2021·Signal Transduction and Targeted Therapy·Jiaxin LiuYong Song
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Methods Mentioned

BETA
ubiquitination
acetylation
neddylation
deubiquitination
nucleotide dissociation
GTPase
xenografts
xenograft
MDS

Clinical Trials Mentioned

NCT02181413
NCT03345095
NCT01549431

Software Mentioned

SidE

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