Sirtuin 7-dependent deacetylation of DDB1 regulates the expression of nuclear receptor TR4

Karim, Md. Fazlul; Yoshizawa, Tatsuya; Sobuz, Shihab U.; Sato, Yuzo; Yamagata, Kazuya

doi:10.1016/j.bbrc.2017.06.057

Cited by 23 publications

(18 citation statements)

References 20 publications

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“…SIRT7 was previously reported to interact with the CRL4-DCAF1 and modulate its ubiquitin ligase activity (11,17,18). Consistent with those findings, in co-immunoprecipitation experiments, we observed an interaction between DCAF1 and SIRT7 ( Fig.…”

Section: Sirt7 Is a Crl4-dcaf1 Binding Proteinsupporting

confidence: 92%

HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7

Zhou

Monnie

DeLucia

et al. 2020

Preprint

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Background: Vpr is a virion-associated protein that is encoded by lentiviruses and serves to counteract intrinsic immunity factors that restrict infection. HIV-1 Vpr mediates proteasome-dependent degradation of several DNA repair/modification proteins. Mechanistically, Vpr directly recruits cellular targets onto DCAF1, a substrate receptor of Cullin 4 RING E3 ubiquitin ligase (CRL4) for poly-ubiquitination. Further, Vpr can mediate poly-ubiquitination of DCAF1-interacting proteins by the CRL4. Because Vpr-mediated degradation of its known targets can not explain the primary cell-cycle arrest phenotype that Vpr expression induces, we surveyed the literature for DNA-repair-associated proteins that interact with the CRL4-DCAF1. One such protein is SIRT7, a deacetylase of histone 3 that belongs to the Sirtuin family and regulates a wide range of cellular processes. We wondered whether Vpr can mediate degradation of SIRT7 via the CRL4-DCAF1. Methods: HEK293T cells were transfected with cocktails of plasmids expressing DCAF1, DDB1, SIRT7 and Vpr. Ectopic and endogeneous levels of SIRT7 were monitered by immunoblotting and protein-protein interactions were assessed by immunoprecipitation. For in vitro reconstitution assays, recombinant CRL4-DCAF1-Vpr complexes and SIRT7 were prepared and poly-ubiqutination of SIRT7 was monitored with immunoblotting. Results: We demonstrate SIRT7 polyubiquitination and degradation upon Vpr expression. Specifically, SIRT7 is shown to interact with the CRL4-DCAF1 complex, and expression of Vpr in HEK293T cells results in SIRT7 degradation, which is partially rescued by CRL inhibitor MNL4924 and proteasome inhibitor MG132. Further, in vitro reconstitution assays show that Vpr induces poly-ubiquitination of SIRT7 by the CRL4-DCAF1. Importantly, we find that Vpr from several different HIV-1 strains, but not HIV-2 strains, mediates SIRT7 poly-ubiquitination in the reconstitution assay and degradation in cells. Finally, we show that SIRT7 degradation by Vpr is independent of the known, distinctive phenotype of Vpr-induced cell cycle arrest at the G2 phase, Conclusions: Targeting histone deacetylase SIRT7 for degradation is a conserved feature of HIV-1 Vpr. Altogether , our findings reveal that HIV-1 Vpr mediates down-regulation of SIRT7 by a mechanism that does not involve novel target recruitment to the CRL4-DCAF1 but instead involves regulation of the E3 ligase activity.

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Section: Sirt7 Is a Crl4-dcaf1 Binding Proteinsupporting

confidence: 92%

HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7

Zhou

Monnie

DeLucia

et al. 2020

Preprint

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“…A pair of recent studies suggest that DCAF1 regulates lipid metabolism (Yoshizawa et al, 2014; Karim et al, 2017). The authors were originally interested in determining the function of Sirtuin-7 (SIRT7) in lipid uptake in the liver (Yoshizawa et al, 2014).…”

Section: Function Of Dcaf1 In Normal Physiology and Cancermentioning

confidence: 99%

DCAF1 (VprBP): emerging physiological roles for a unique dual-service E3 ubiquitin ligase substrate receptor

Schabla

Mondal

Swanson

2018

Journal of Molecular Cell Biology

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Cullin-RING ligases (CRLs) comprise a large group of modular eukaryotic E3 ubiquitin ligases. Within this family, the CRL4 ligase (consisting of the Cullin4 [CUL4] scaffold protein, the Rbx1 RING finger domain protein, the DNA damage-binding protein 1 [DDB1], and one of many DDB1-associated substrate receptor proteins) has been intensively studied in recent years due to its involvement in regulating various cellular processes, its role in cancer development and progression, and its subversion by viral accessory proteins. Initially discovered as a target for hijacking by the human immunodeficiency virus accessory protein r, the normal targets and function of the CRL4 substrate receptor protein DDB1–Cul4-associated factor 1 (DCAF1; also known as VprBP) had remained elusive, but newer studies have begun to shed light on these questions. Here, we review recent progress in understanding the diverse physiological roles of this DCAF1 in supporting various general and cell type-specific cellular processes in its context with the CRL4 E3 ligase, as well as another HECT-type E3 ligase with which DCAF1 also associates, called EDD/UBR5. We also discuss emerging questions and areas of future study to uncover the dynamic roles of DCAF1 in normal physiology.

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“…Li et al observed that SIRT1/SIRT7 deacetylate FOXO3 in vitro and in vivo to prevent its phosphorylation and block apoptosis in response to lipopolysaccharide stimulation ( 18 ). Mo et al found that SIRT7 is a major deacetylase of DNA damage-binding protein 1 (DDB1): DDB1 acetylation negatively regulates the DDB1–CUL4 interaction and CRL4 activity ( 19 , 20 ). Tang et al found that SIRT7 inhibits breast cancer lung metastasis by deacetylating and promoting SMAD4 degradation ( 21 ).…”

Section: Sirt7 Enzymatic Activitymentioning

confidence: 99%

“…Conomos et al found that TR4 recruitment to the telomere can attribute to the ALT (alternative lengthening of telomeres) phenotype ( 72 ). SIRT7 positively regulates the protein level of TR4 ( 19 ), suggesting that SIRT7 might play an upstream role in DNA repair and telomere maintenance pathways.…”

Section: Sirt7 Biological Functionsmentioning

confidence: 99%

Advances in Cellular Characterization of the Sirtuin Isoform, SIRT7

Zhu

et al. 2018

Front. Endocrinol.

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SIRT7 is one of seven mammalian sirtuins that functions as an NAD+-dependent histone/protein deacetylase. SIRT7 is the least well-known member of the sirtuin family, but recent efforts have identified its involvement in various cellular processes, such as ribosome biogenesis, gene expression, cellular metabolism and cancer. Here we provide an update on the functions and mechanisms of SIRT7 in cellular regulation and disease.

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Sirtuin 7-dependent deacetylation of DDB1 regulates the expression of nuclear receptor TR4

Cited by 23 publications

References 20 publications

HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7

HIV-1 Vpr activates host CRL4-DCAF1 E3 ligase to degrade histone deacetylase SIRT7

DCAF1 (VprBP): emerging physiological roles for a unique dual-service E3 ubiquitin ligase substrate receptor

Advances in Cellular Characterization of the Sirtuin Isoform, SIRT7

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