De-repression of RaRF-mediated RAR repression by adenovirus E1A in the nucleolus

Um, Soo‐Jong; Youn, Hye Sook; Kim, Eun-Joo

doi:10.1016/j.bbrc.2014.01.105

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…Nucleolar integrity and ribosomal RNA (rRNA) transcription are tightly coupled, with inhibition of rRNA transcription favoring protein translocation from the nucleolus to the nucleoplasm (Iarovaia et al, 2019). CCDC137 was first identified to be a retinoic acid resistance factor (RaRF) that is responsible for sequestering the retinoic acid receptor (RAR) within the nucleolus (Um et al, 2014). CCDC137 was later found to associate with another nuclear receptor, estrogen related receptor alpha (ERRa), and sequester ERRa within the nucleolus (Um et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Nucleolar proteins are often redistributed during viral infection, including HIV-1 infection (reviewed in (Salvetti and Greco, 2014)). CCDC137 is antagonized by another viral protein, adenovirus E1A protein, that was shown to disrupt CCDC137 association with RAR, which results in release of RAR into the nucleoplasm and increased transcription of RAR target genes (Um et al, 2014). Recently, Vpr has been shown to target sirtuin 7 (SIRT7), a protein that resides predominantly in the nucleolus (Zhou et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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HIV-1 Vpr Induces Degradation of Nucleolar Protein CCDC137 as a Consequence of Cell Cycle Arrest

Martins

DePaula-Silva

Planelles

2021

Preprint

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Expression of HIV-1 accessory proteins Vif and Vpr results in G2/M cell cycle arrest by hijacking the host ubiquitin-proteasome system. Vif directs cell cycle arrest by targeting protein phosphatase 2, regulatory subunit B alpha (PP2AB56) for degradation. However, the ubiquitination target(s) of Vpr that is directly responsible for G2/M arrest has remained elusive. Recently, Vpr directed degradation of nucleolar protein coiled-coil domain containing 137 (CCDC137), also known as retinoic acid resistance factor (RaRF), has been implicated as the proximal event leading to G2/M cell cycle arrest. In this study we aimed to further investigate this finding. We confirm that CCDC137 is targeted for degradation in the presence of Vpr with a requirement for the CUL4ADDB1.DCAF1 E3 ligase complex. However, degradation of CCDC137 is a general consequence, rather than a trigger, of G2/M arrest. Thus, whether induced by Vpr expression or pharmacologically via CDK1 inhibition, G2/M blockade results in degradation of CCDC137. Furthermore, siRNA-mediated depletion of CCDC137 failed to induce G2/M arrest.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HIV-1 Vpr Induces Degradation of Nucleolar Protein CCDC137 as a Consequence of Cell Cycle Arrest

Martins

DePaula-Silva

Planelles

2021

Preprint

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RaRF confers RA resistance by sequestering RAR to the nucleolus and regulating MCL1 in leukemia cells

Youn

Lee

et al. 2017

Oncogene

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Retinoic acid (RA) has broad clinical applications for the treatment of various cancers, particularly acute promyelocytic leukemia. However, RA-based therapy is limited by relapse in patients associated with RA resistance, the mechanism of which is poorly understood. Here, we suggest a new molecular mechanism of RA resistance by a repressor, named RA resistance factor (RaRF). RaRF suppressed transcriptional activity of the RA receptor (RAR) by directly interacting with and sequestering RAR to the nucleolus in response to RA. RaRF was highly expressed in RA-resistant leukemia cells and its expression was strongly correlated with RA sensitivity. MCL1 was upregulated by RA treatment upon RaRF depletion, accompanying leukemic myeloblast differentiation, which is negatively regulated by ectopic RaRF expression. Collectively, we propose that RaRF may be a factor in the resistance mechanism and thus a potential target for leukemia therapy using RA.

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De-repression of RaRF-mediated RAR repression by adenovirus E1A in the nucleolus

Cited by 2 publications

References 27 publications

HIV-1 Vpr Induces Degradation of Nucleolar Protein CCDC137 as a Consequence of Cell Cycle Arrest

HIV-1 Vpr Induces Degradation of Nucleolar Protein CCDC137 as a Consequence of Cell Cycle Arrest

RaRF confers RA resistance by sequestering RAR to the nucleolus and regulating MCL1 in leukemia cells

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