The Biology of F-box Proteins: The SCF Family of E3 Ubiquitin Ligases

Nguyen, Khai M.; Busino, Luca

doi:10.1007/978-981-15-1025-0_8

Cited by 58 publications

(45 citation statements)

References 79 publications

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“…pneumophila harbors at least five effectors that harbor the eukaryotic F-box domain [57,61,62]. In humans there are at least 70 F-box proteins [63], indicating that regulation of protein ubiquitination by the SCF ligase machinery is a key mechanism controlling protein fate in eukaryotic cells. In eukaryotes, F-box proteins form part of a multi-protein complex designated the E3 SCF-ubiquitin ligase [63].…”

Section: F-box Effectorsmentioning

confidence: 99%

“…In humans there are at least 70 F-box proteins [63], indicating that regulation of protein ubiquitination by the SCF ligase machinery is a key mechanism controlling protein fate in eukaryotic cells. In eukaryotes, F-box proteins form part of a multi-protein complex designated the E3 SCF-ubiquitin ligase [63]. The SCF-ligase complex is composed of a RING-domain protein RING-box 1 (RBX1), cullin 1 (CUL1), S-phase-kinase associated protein 1 (SKP1) and a protein harboring an F-box domain, that directly binds SKP1 [63].…”

Section: F-box Effectorsmentioning

confidence: 99%

“…In eukaryotes, F-box proteins form part of a multi-protein complex designated the E3 SCF-ubiquitin ligase [63]. The SCF-ligase complex is composed of a RING-domain protein RING-box 1 (RBX1), cullin 1 (CUL1), S-phase-kinase associated protein 1 (SKP1) and a protein harboring an F-box domain, that directly binds SKP1 [63]. The associated F-box protein determines the specificity of the ubiquitination event by binding to target proteins through protein-protein interaction domains.…”

Section: F-box Effectorsmentioning

confidence: 99%

“…The associated F-box protein determines the specificity of the ubiquitination event by binding to target proteins through protein-protein interaction domains. [63]. In higher eukaryotes, F-box proteins are classified into three subfamilies on the basis of the proteinprotein interaction domains they possess and include; those with leucine-rich repeats (FBXL), WD40 repeats (FBXW) or uncharacterized domains (FBXO) [64].…”

Section: F-box Effectorsmentioning

confidence: 99%

See 3 more Smart Citations

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

Price

Kwaik

2021

Biomolecules

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The ubiquitin pathway is highly conserved across the eukaryotic domain of life and plays an essential role in a plethora of cellular processes. It is not surprising that many intracellular bacterial pathogens often target the essential host ubiquitin pathway. The intracellular bacterial pathogen Legionella pneumophila injects into the host cell cytosol multiple classes of classical and novel ubiquitin-modifying enzymes that modulate diverse ubiquitin-related processes in the host cell. Most of these pathogen-injected proteins, designated as effectors, mimic known E3-ubiquitin ligases through harboring F-box or U-box domains. The classical F-box effector, AnkB targets host proteins for K48-linked polyubiquitination, which leads to excessive proteasomal degradation that is required to generate adequate supplies of amino acids for metabolism of the pathogen. In contrast, the SidC and SdcA effectors share no structural similarity to known eukaryotic ligases despite having E3-ubiquitin ligase activity, suggesting that the number of E3-ligases in eukaryotes is under-represented. L. pneumophila also injects into the host many novel ubiquitin-modifying enzymes, which are the SidE family of effectors that catalyze phosphoribosyl-ubiquitination of serine residue of target proteins, independently of the canonical E1-2-3 enzymatic cascade. Interestingly, the environmental bacterium, L. pneumophila, has evolved within a diverse range of amoebal species, which serve as the natural hosts, while accidental transmission through contaminated aerosols can cause pneumonia in humans. Therefore, it is likely that the novel ubiquitin-modifying enzymes of L. pneumophila were acquired by the pathogen through interkingdom gene transfer from the diverse natural amoebal hosts. Furthermore, conservation of the ubiquitin pathway across eukaryotes has enabled these novel ubiquitin-modifying enzymes to function similarly in mammalian cells. Studies on the biological functions of these effectors are likely to reveal further novel ubiquitin biology and shed further lights on the evolution of ubiquitin.

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Section: F-box Effectorsmentioning

confidence: 99%

Section: F-box Effectorsmentioning

confidence: 99%

Section: F-box Effectorsmentioning

confidence: 99%

Section: F-box Effectorsmentioning

confidence: 99%

See 2 more Smart Citations

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

Price

Kwaik

2021

Biomolecules

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“…F-box proteins have been validated to play a pivotal role in carcinogenesis and progression 13 , 15 . They are involved in various physiological and pathological processes which include proliferation, apoptosis, metastasis, cancer stem cell generation, epithelial–mesenchymal transition (EMT), drug resistance in human cancers 16 – 18 . It is important to notice that F-box proteins, including FBXO22, have oncogenic or tumor suppressive role in cancer development and progression.…”

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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Regulation of nutrient utilization in filamentous fungi

Kerkaert

Huberman

2023

Appl Microbiol Biotechnol

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The Biology of F-box Proteins: The SCF Family of E3 Ubiquitin Ligases

Cited by 58 publications

References 79 publications

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

Evolution and Adaptation of Legionella pneumophila to Manipulate the Ubiquitination Machinery of Its Amoebae and Mammalian Hosts

Emerging role of FBXO22 in carcinogenesis

Regulation of nutrient utilization in filamentous fungi

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