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Published on: April 2, 2020
The characteristics and roles of β-TrCP1/2 in carcinogenesis
Yanli Bi1,2, Danrui Cui1,2, Xiufang Xiong2,3
1Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract:
β-transducin repeat-containing protein (β-TrCP), one of the well-characterized F-box proteins, acts as a substrate receptor and constitutes an active SCFβ-TrCP E3 ligase with a scaffold protein CUL1, a RING protein RBX1, and an adaptor protein SKP1. β-TrCP plays a critical role in the regulation of various physiological and pathological processes, including signal transduction, cell cycle progression, cell migration, DNA damage response, and tumorigenesis, by governing burgeoning amounts of key regulators for ubiquitination and proteasomal degradation. Given that a variety of β-TrCP substrates are well-known oncoproteins and tumor suppressors, and dysregulation of β-TrCP is frequently identified in human cancers, β-TrCP plays a vital role in carcinogenesis. In this review, we first briefly introduce the characteristics of β-TrCP1, β-TrCP2, and SCFβ-TrCP ubiquitin ligase, and then discuss SCFβ-TrCP ubiquitin ligase regulated biological processes by targeting its substrates for degradation. Moreover, we summarize the regulation of β-TrCP1 and β-TrCP2 at multiple layers and further discuss the various roles of β-TrCP1 and β-TrCP2 in human cancer, functioning as either an oncoprotein or a tumor suppressor in a manner dependent of cellular context. Finally, we provide novel insights for future perspectives on the potential of targeting β-TrCP1 and β-TrCP2 for cancer therapy.
Insights
Beta-transducin repeat-containing protein (β-TrCP) is crucial in regulating cell processes and is implicated in cancer. Targeting β-TrCP offers potential for novel cancer therapies.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- β-transducin repeat-containing protein (β-TrCP) is an F-box protein acting as a substrate receptor in the SCFβ-TrCP E3 ubiquitin ligase complex.
- β-TrCP regulates critical physiological and pathological processes, including cell cycle, DNA damage response, and tumorigenesis, by controlling protein degradation.
Purpose of the Study:
- To review the characteristics of β-TrCP1, β-TrCP2, and the SCFβ-TrCP ubiquitin ligase.
- To discuss the biological processes regulated by SCFβ-TrCP through substrate degradation.
- To summarize the multi-layered regulation of β-TrCP1 and β-TrCP2 and their roles in human cancers.
Main Methods:
- Literature review of β-TrCP function, regulation, and roles in cancer.
- Analysis of β-TrCP's involvement in ubiquitination and proteasomal degradation pathways.
- Synthesis of current knowledge on β-TrCP as an oncoprotein or tumor suppressor.
Main Results:
- β-TrCP ligase complex targets key regulators for ubiquitination and proteasomal degradation.
- Dysregulation of β-TrCP is frequently observed in human cancers, highlighting its role in carcinogenesis.
- β-TrCP1 and β-TrCP2 function context-dependently as either oncoproteins or tumor suppressors.
Conclusions:
- β-TrCP plays a pivotal role in human cancer development and progression.
- Understanding β-TrCP regulation and function provides insights into cancer biology.
- Targeting β-TrCP1 and β-TrCP2 presents a promising avenue for developing new cancer therapeutics.
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