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

Martins, L. J.; DePaula-Silva, A. B.; Planelles, V.

doi:10.1101/2021.03.16.435666

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bioRxiv · 10.1101/2021.03.16.435666

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

Martins, L. J.·DePaula-Silva, A. B.·Planelles, V.

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Abstract

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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Martins, L. J., DePaula-Silva, A. B., Planelles, V.. 2021-03-16. HIV-1 Vpr Induces Degradation of Nucleolar Protein CCDC137 as a Consequence of Cell Cycle Arrest. https://doi.org/10.1101/2021.03.16.435666

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