Cullin-RING E3 Ubiquitin Ligases: Bridges to Destruction

Nguyen, Henry C.; Wang, Wei; Xiong, Yong

doi:10.1007/978-3-319-46503-6_12

Cited by 54 publications

(47 citation statements)

References 106 publications

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“…Analyses of these interactors via the String database (Szklarczyk et al, 2017) grouped the interactions into functionally associated pathways and protein complexes (Fig 5B). Among the most significantinteractors, were the known subunits of E3 ubiquitin ligase complex including Cullin 2 (Cul2), Elongin C (EloC), Elongin B (EloB), and Ring-box protein 1 (Rbx1) (marked with asterisk in Fig 5A and highlighted in yellow in Fig 5B), which together form a Cul2-E3 ubiquitin ligase (Nguyen et al, 2017). …”

Section: Resultsmentioning

confidence: 99%

A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability

Nayak¹,

Kim²,

Trnka³

et al. 2018

Cell Host & Microbe

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Summary The dicistrovirus, Cricket paralysis virus (CrPV) encodes an RNA interference (RNAi) suppressor, 1A, which modulates viral virulence. Using the Drosophila model, we combined structural, biochemical, and virological approaches to elucidate the strategies by which CrPV-1A restricts RNAi immunity. The atomic resolution structure of CrPV-1A uncovered a flexible loop that interacts with Argonaute 2 (Ago-2), thereby inhibiting Ago-2 endonuclease-dependent immunity. Mutations disrupting Ago-2-binding attenuates viral pathogenesis in wild-type but not Ago-2-deficient flies. CrPV-1A also contains a BC-box motif that enables the virus to hijack a host Cul2-Rbx1-EloBC ubiquitin ligase complex, which promotes Ago-2 degradation and virus replication. Our study uncovers a viral-based dual regulatory program that restricts antiviral immunity by direct interaction with and modulation of host proteins. While the direct inhibition of Ago-2 activity provides an efficient mechanism to establish infection, the recruitment of a ubiquitin ligase complex, enables CrPV-1A to amplify Ago-2 inactivation to restrict further antiviral RNAi immunity.

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Section: Resultsmentioning

confidence: 99%

A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability

Nayak¹,

Kim²,

Trnka³

et al. 2018

Cell Host & Microbe

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“…Counting over 200 members in mammalian cells, CRLs represent the largest group of RING E3 ligases and control approximately 20% of cellular ubiquitination. Through activation of CRL activity, NEDD8 regulates a wide range of essential processes mediated by CRL substrates, including cell cycle progression, growth and differentiation, stress responses, DNA repair, and cell signalling [ 96 , 97 ]. Although a number of non-Cullin substrates have been reported, such as some E3 ubiquitin ligases, transcription factors, and ribosomal proteins, not all of them are backed by strong experimental evidence due to their use of NEDD8 overexpression [ 98 , 99 ].…”

Section: Nedd8: Still a Mysterymentioning

confidence: 99%

Ubiquitin-Like Modifiers: Emerging Regulators of Protozoan Parasites

Karpiyevich

Artavanis‐Tsakonas

2020

Biomolecules

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Post-translational protein regulation allows for fine-tuning of cellular functions and involves a wide range of modifications, including ubiquitin and ubiquitin-like modifiers (Ubls). The dynamic balance of Ubl conjugation and removal shapes the fates of target substrates, in turn modulating various cellular processes. The mechanistic aspects of Ubl pathways and their biological roles have been largely established in yeast, plants, and mammalian cells. However, these modifiers may be utilised differently in highly specialised and divergent organisms, such as parasitic protozoa. In this review, we explore how these parasites employ Ubls, in particular SUMO, NEDD8, ATG8, ATG12, URM1, and UFM1, to regulate their unconventional cellular physiology. We discuss emerging data that provide evidence of Ubl-mediated regulation of unique parasite-specific processes, as well as the distinctive features of Ubl pathways in parasitic protozoa. We also highlight the potential to leverage these essential regulators and their cognate enzymatic machinery for development of therapeutics to protect against the diseases caused by protozoan parasites.

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“…E3 ligases recognize and recruit the target protein for ubiquitination, thus they were extensively characterized 8 . Among E3 ligases, Cullin-RING E3 ligase (CRL) complex is one of the largest families, including CRL1–3, 4A, 4B, 5, 7, and 9 9 – 11 . CRL1, also known as SKP1-cullin 1-F-box protein (SCF) E3 ligase complex, contains cullin-1 acting as the scaffold protein, RBX1 for recruiting ubiquitin-loaded E2, SKP1 working as an adaptor protein to connect F-box protein, and F-box protein for selecting substrates for degradation 12 .…”

Section: Introductionmentioning

confidence: 99%

Emerging role of FBXO22 in carcinogenesis

et al. 2020

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The F-box protein 22 (FBXO22), one of F-box proteins, has been identified to be critically involved in carcinogenesis. FBXO22 promotes proliferation in breast cancer and lung cancer, but suppresses migration and metastasis. FBXO22 exerts oncogenetic functions via promoting the ubiquitination and degradation of its substrates, including KDM4A, KDM4B, methylated p53, p21, KLF4, LKB1, Snail, CD147, Bach1, PTEN, and HDM2. FBXO22 is also regulated by several regulatory factors such as p53, miR-155, SNHG14, and circ_0006282. In this review, we summarize the regulatory factors and downstream targets of FBXO22 in cancers, discuss its functions in tumorigenesis, and further highlight the alteration of FBXO22 expression in a variety of human malignancies. Finally, we provide novel insights for future perspectives on targeting FBXO22 as a promising strategy for cancer therapy. Facts FBXO22 targets multiple substrates for ubiquitination and degradation. FBXO22 is critically involved in tumorigenesis and tumor progression. FBXO22 might be a therapeutic target for cancer treatment. Open questions Which targets of FBXO22 are pivotal for cancer development and malignant progression? Do E3 liagses regulate the protein levels of FBXO22? How the inhibitors of FBXO22 could be developed and discovered for cancer therapy?

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Cullin-RING E3 Ubiquitin Ligases: Bridges to Destruction

Cited by 54 publications

References 106 publications

A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability

A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability

Ubiquitin-Like Modifiers: Emerging Regulators of Protozoan Parasites

Emerging role of FBXO22 in carcinogenesis

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