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

Youn, HyeSook; Lee, Hye Kyung; Hr, Sohn; Uh, Park; Ej, Kim; Youn, BuHyun; Sj, Um

doi:10.1038/onc.2017.329

Cited by 4 publications

(2 citation statements)

References 52 publications

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“…1E, Fig. S3B) and alanine substitutions of an LxxLL motif (positions 228-232) through which CCDC137 binds nuclear receptors (33), also reduced Vpr-induced CCDC137 depletion (L/A, mutation, Fig. 1E).…”

Section: Discussionmentioning

confidence: 93%

HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137

Zhang

Bieniasz

2019

Preprint

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The HIV-1 Vpr accessory protein induces ubiquitin/proteasome-dependent degradation of many cellular proteins by recruiting them to a cullin4A-DDB1-DCAF1 complex. In so doing, Vpr enhances HIV-1 gene expression and induces (G2/M) cell cycle arrest. However, the identities of Vpr target proteins through which these biological effects are exerted are unknown. We show that a chromosome periphery protein, CCDC137/cPERP-B, is targeted for depletion by HIV-1 Vpr, in a cullin4A-DDB1-DCAF1 dependent manner. CCDC137 depletion caused G2/M cell-cycle arrest, while Vpr-resistant CCDC137 mutants conferred resistance to Vpr-induced G2/M arrest. CCDC137 depletion also recapitulated the ability of Vpr to enhance HIV-1 gene expression, particularly in macrophages. Our findings indicate that Vpr promotes cell-cycle arrest and HIV-1 gene expression through depletion of CCDC137.

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Section: Discussionmentioning

confidence: 93%

HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137

Zhang

Bieniasz

2019

Preprint

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“…MCL-1-mediated chemotherapy resistance was attributed to resistance to apoptotic cell death or compromised homologous recombination-mediated DNA double-strand break repair [ 41 ]. Furthermore, the correlation between MCL-1 overexpression and stem cell-like potential has been reported previously in several cancer types, such as breast cancer [ 42 ], leukemia [ 43 , 44 ], lung cancer [ 45 ], and glioblastoma [ 46 ]. In our study, we examined an additional role for MCL-1 in irradiation-induced cancer stem-like cells and acquired radioresistance in NPC.…”

Section: Discussionmentioning

confidence: 70%

Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop

Liang

Niu

et al. 2022

Cell Death Dis

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Worldwide, nasopharyngeal carcinoma (NPC) is a rare head and neck cancer; however, it is a common malignancy in southern China. Radiotherapy is the most important treatment strategy for NPC. However, although radiotherapy is a strong tool to kill cancer cells, paradoxically it also promotes aggressive phenotypes. Therefore, we mimicked the treatment process in NPC cells in vitro. Upon exposure to radiation, a subpopulation of NPC cells gradually developed resistance to radiation and displayed cancer stem-cell characteristics. Radiation-induced stemness largely depends on the accumulation of the antiapoptotic myeloid cell leukemia 1 (MCL-1) protein. Upregulated MCL-1 levels were caused by increased stability and more importantly, enhanced protein synthesis. We showed that repeated ionizing radiation resulted in persistently enhanced reactive oxygen species (ROS) production at a higher basal level, further promoting protein kinase B (AKT) signaling activation. Intracellular ROS and AKT activation form a positive feedback loop in the process of MCL-1 protein synthesis, which in turn induces stemness and radioresistance. AKT/MCL-1 axis inhibition attenuated radiation-induced resistance, providing a potential target to reverse radiation therapy-induced radioresistance.

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CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X

Dobransky,

Root,

Hafner

et al. 2024

Viruses

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The Human Immunodeficiency Virus (HIV) encodes several proteins that contort the host cell environment to promote viral replication and spread. This is often accomplished through the hijacking of cellular ubiquitin ligases. These reprogrammed complexes initiate or enhance the ubiquitination of cellular proteins that may otherwise act to restrain viral replication. Ubiquitination of target proteins may alter protein function or initiate proteasome-dependent destruction. HIV Viral Protein R (Vpr) and the related HIV-2 Viral Protein X (Vpx), engage the CRL4-DCAF1 ubiquitin ligase complex to target numerous cellular proteins. In this review we describe the CRL4-DCAF1 ubiquitin ligase complex and its interactions with HIV Vpr and Vpx. We additionally summarize the cellular proteins targeted by this association as well as the observed or hypothesized impact on HIV.

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

Cited by 4 publications

References 52 publications

HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137

HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137

Increased MCL-1 synthesis promotes irradiation-induced nasopharyngeal carcinoma radioresistance via regulation of the ROS/AKT loop

CRL4-DCAF1 Ubiquitin Ligase Dependent Functions of HIV Viral Protein R and Viral Protein X

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