The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression

Zou, Tingting; Lin, Zhenghong

doi:10.3390/ijms22115754

Cited by 68 publications

(47 citation statements)

References 236 publications

(284 reference statements)

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“…A majority of intracellular proteins are modified by ubiquitination ( Amm et al, 2014 ). Several Ub signals are recognized by proteasomes, thereby serving as a regulatory mechanism for protein degradation, affecting nearly all aspects of cellular processes ( Chowdhury and Enenkel, 2015 ; Hanna et al, 2019 ; Sakai et al, 2020 ; Fhu and Ali, 2021 ; Goetzke et al, 2021 ; Qu et al, 2021 ; Zou and Lin, 2021 ). Ubiquitin signaling is strictly regulated by a multistep cascade reaction consisting of three enzyme groups.…”

Section: Introductionmentioning

confidence: 99%

Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

Wang

Sun

et al. 2021

Front. Cell Dev. Biol.

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Ubiquitination is a posttranslational modification of proteins that significantly affects protein stability and function. The specificity of substrate recognition is determined by ubiquitin E3 ligase during ubiquitination. Human Deltex (DTX) protein family, which functions as ubiquitin E3 ligases, comprises five members, namely, DTX1, DTX2, DTX3, DTX3L, and DTX4. The characteristics and functional diversity of the DTX family proteins have attracted significant attention over the last decade. DTX proteins have several physiological and pathological roles and are closely associated with cell signal transduction, growth, differentiation, and apoptosis, as well as the occurrence and development of various tumors. Although they have been extensively studied in various species, data on structural features, biological functions, and potential mechanisms of action of the DTX family proteins remain limited. In this review, recent research progress on each member of the DTX family is summarized, providing insights into future research directions and potential strategies in disease diagnosis and therapy.

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Section: Introductionmentioning

confidence: 99%

Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

Wang

Sun

et al. 2021

Front. Cell Dev. Biol.

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“…MiRNAs are central regulators of biological events. And ubiquitin–proteasome systems are also involved in almost all cell signaling regulation such as cell cycle, cell proliferation, apoptosis, and autophagy [ 163 , 164 , 165 ]. Here, we illustrate the important impact of crosstalk between miRNA and UPS in autophagy regulation due to the increasingly important impact status of autophagy in malignant diseases such as tumors today.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Regulation by Crosstalk between miRNAs and Ubiquitination System

Lin

2021

IJMS

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MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes with ~22 nucleotides which are involved in the regulation of post-transcriptional gene expression. Ubiquitination and deubiquitination are common post-translational modifications in eukaryotic cells and important pathways in regulating protein degradation and signal transduction, in which E3 ubiquitin ligases and deubiquitinases (DUBs) play a decisive role. MiRNA and ubiquitination are involved in the regulation of most biological processes, including autophagy. Furthermore, in recent years, the direct interaction between miRNA and E3 ubiquitin ligases or deubiquitinases has attracted much attention, and the cross-talk between miRNA and ubiquitination system has been proved to play key regulatory roles in a variety of diseases. In this review, we summarized the advances in autophagy regulation by crosstalk between miRNA and E3 ubiquitin ligases or deubiquitinases.

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“…Three of the seven β-subunits are catalytically active and provide proteolytic activity of the proteasome: β1-subunit has caspase-like activity (CL), β2-subunit has trypsin-like activity (TL), and β5-subunit demonstrates chymotrypsinlike activity (ChTL) [3,4]. Dysfunction of this complex can lead to regulatory proteins be stabilized due to reduced degradation or lost due to accelerated degradation [5]. Previous research has shown that tissue proteasome activity is associated with cancer progression and can be used to stratify risk [6,7].…”

Section: Introductionmentioning

confidence: 99%

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

et al. 2021

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Exosomes are directly involved in governing of physiological and pathological conditions of an organism through the transfer of information from producing to receiving cells. It can be assumed that exosomes are one of the key players of tumor dissemination since they are very stable and small enough to penetrate from various tissues into biological fluids and then back, thus interacting with tissue target cells. We evaluated the enzymatic activity and the level of 20S proteasome in tissue and exosomes of healthy females (n = 39) and patients with ovarian (n = 50) and breast (n = 108) tumors to reveal the critical role of exosomal cargo in the mediation of different types of metastases. Exosomes from plasma and ascites were isolated and characterized in according to International Society for Extracellular Vesicles guidelines. The level of 20S proteasome in tissue and exosomes was determined using Western blot analysis. Chymotrypsin- and caspase-like (ChTL and CL, respectively) peptidase activities of the proteasomes were determined using fluorogenic Suc-LLVY-AMC and Cbz-LLG-AMC substrates, respectively. We observed increased levels of 20S proteasome in ovarian cancer tissue and luminal B subtype breast cancer tissue as well as in plasma exosomes from cancer patients. Moreover, the level of the 20S proteasome in plasma exosomes and ascites exosomes in patients with ovarian tumors is comparable and higher in ovarian cancer patients with low volume ascites than in patients with moderate and high-volume ascites. We also found increased ChTL and CL activities in breast cancer and ovarian cancer tissues, as well as in peritoneal metastases in ovarian cancer, while proteasomal activity in exosomes from plasma of healthy females and all patients, as well as from ascites of ovarian tumor patients were lower than detection limit of assay. Thus, regardless of the type of tumor metastasis (lymphogenous or peritoneal), the exosomes of cancer patients were characterized by an increased level of 20S proteasome, which do not exhibit enzymatic activity.

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The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression

Cited by 68 publications

References 236 publications

Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

Functions and Molecular Mechanisms of Deltex Family Ubiquitin E3 Ligases in Development and Disease

Autophagy Regulation by Crosstalk between miRNAs and Ubiquitination System

Plasma Exosomes of Patients with Breast and Ovarian Tumors Contain an Inactive 20S Proteasome

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