Ubiquitin Ligases: Structure, Function, and Regulation

Annual Review of Biochemistry, Journal Year: 2017, Volume and Issue: 86(1), P. 129 - 157

Published: April 4, 2017

Ubiquitin E3 ligases control every aspect of eukaryotic biology by promoting protein ubiquitination and degradation. At the end a three-enzyme cascade, ubiquitin mediate transfer from an E2 ubiquitin-conjugating enzyme to specific substrate proteins. Early investigations E3s RING (really interesting new gene) HECT (homologous E6AP carboxyl terminus) types shed light on their enzymatic activities, general architectures, degron-binding modes. Recent studies have provided deeper mechanistic insights into catalysis, activation, regulation. In this review, we summarize current progress in structure-function as well exciting discoveries novel classes diverse recognition mechanisms. Our increased understanding ligase function regulation has rationale for developing E3-targeting therapeutics treatment human diseases.

Language: Английский

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Recognition of Endogenous Nucleic Acids by the Innate Immune System

Immunity, Journal Year: 2016, Volume and Issue: 44(4), P. 739 - 754

Published: April 1, 2016

Language: Английский

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Bat-borne virus diversity, spillover and emergence

Nature Reviews Microbiology, Journal Year: 2020, Volume and Issue: 18(8), P. 461 - 471

Published: June 11, 2020

Language: Английский

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Advancing targeted protein degradation for cancer therapy

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(10), P. 638 - 654

Published: June 15, 2021

Language: Английский

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Restricting retrotransposons: a review

Mobile DNA, Journal Year: 2016, Volume and Issue: 7(1)

Published: Aug. 11, 2016

Retrotransposons have generated about 40 % of the human genome. This review examines strategies cell has evolved to coexist with these genomic "parasites", focussing on non-long terminal repeat retrotransposons humans and mice. Some restriction factors for retrotransposition, including APOBECs, MOV10, RNASEL, SAMHD1, TREX1, ZAP, also limit replication retroviruses, HIV, are part intrinsic immune system cell. Many proteins act in cytoplasm degrade retroelement RNA or inhibit its translation. nucleus involve DNA repair enzymes epigenetic processes methylation histone modification. RISC piRNA pathway protect germline. Retrotransposon control is relaxed some types, such as neurons brain, stem cells, certain types disease cancer, implications health disease. considers potential pitfalls interpreting retrotransposon-related data, well issues consider future research.

Language: Английский

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Nucleic Acid Immunity

Advances in immunology, Journal Year: 2016, Volume and Issue: unknown, P. 121 - 169

Published: Dec. 15, 2016

Language: Английский

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Structural basis for targeted DNA cytosine deamination and mutagenesis by APOBEC3A and APOBEC3B

Nature Structural & Molecular Biology, Journal Year: 2016, Volume and Issue: 24(2), P. 131 - 139

Published: Dec. 19, 2016

Language: Английский

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The DNA cytosine deaminase APOBEC3B promotes tamoxifen resistance in ER-positive breast cancer

Science Advances, Journal Year: 2016, Volume and Issue: 2(10)

Published: Oct. 7, 2016

An antiviral enzyme promotes drug resistance in breast cancer.

Language: Английский

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Innate immunity against HIV-1 infection

Nature Immunology, Journal Year: 2015, Volume and Issue: 16(6), P. 554 - 562

Published: May 19, 2015

Language: Английский

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The DNA cytosine deaminase APOBEC3H haplotype I likely contributes to breast and lung cancer mutagenesis

Nature Communications, Journal Year: 2016, Volume and Issue: 7(1)

Published: Sept. 21, 2016

Cytosine mutations within TCA/T motifs are common in cancer. A likely cause is the DNA cytosine deaminase APOBEC3B (A3B). However, A3B-null breast tumours still have this mutational bias. Here we show that APOBEC3H haplotype I (A3H-I) provides a solution to paradox. with bias at least one copy of A3H-I despite little genetic linkage between these genes. Although deemed inactive previously, has robust activity biochemical and cellular assays, similar A3H-II after compensation for lower protein expression levels. Gly105 (versus Arg105 A3H-II) results levels increased nuclear localization, providing mechanism accessing genomic DNA. also associates clonal TCA/T-biased lung adenocarcinoma suggesting enzyme makes broader contributions cancer mutagenesis. These studies combine suggest A3B A3H-I, together, explain bulk 'APOBEC signature'

Language: Английский

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