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Article

The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol

by
Dooti Kundu
,
Xiao Min
,
Xiaohan Zhang
,
Xinru Tian
,
Shujie Wang
and
Kyeong-Man Kim
*
Department of Pharmacology, College of Pharmacy, Chonnam National University, Gwang-Ju 61186, Republic of Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(17), 9644; https://doi.org/10.3390/ijms25179644
Submission received: 28 May 2024 / Revised: 26 August 2024 / Accepted: 4 September 2024 / Published: 6 September 2024
(This article belongs to the Section Molecular Pharmacology)
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Abstract

GRK2 and arrestin3, key players in the functional regulation of G protein-coupled receptors (GPCRs), are ubiquitinated by Mdm2, a nuclear protein. The agonist-induced increase in arrestin3 ubiquitination occurs in the nucleus, underscoring the crucial role of its nuclear translocation in this process. The ubiquitination of arrestin3 occurs in the nucleus, highlighting the pivotal role of its nuclear translocation in this process. In contrast, GRK2 cannot translocate into the nucleus; thus, facilitation of the cytosolic translocation of nuclear Mdm2 is required to ubiquitinate GRK2 in the cytosol. Among the explored cellular components and processes, arrestin, Gβγ, clathrin, and receptor phosphorylation were found to be required for the nuclear import of arrestin3, the ubiquitination of arrestin3 in the nucleus, nuclear export of Mdm2, and the ubiquitination of GRK2 in the cytosol. In conclusion, our findings demonstrate that agonist-induced ubiquitination of arrestin3 in the nucleus is interconnected with cytosolic GRK2 ubiquitination.
Keywords: Mdm2; arrestin; GRK2; ubiquitination; Gβγ; clathrin Mdm2; arrestin; GRK2; ubiquitination; Gβγ; clathrin

Share and Cite

MDPI and ACS Style

Kundu, D.; Min, X.; Zhang, X.; Tian, X.; Wang, S.; Kim, K.-M. The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol. Int. J. Mol. Sci. 2024, 25, 9644. https://doi.org/10.3390/ijms25179644

AMA Style

Kundu D, Min X, Zhang X, Tian X, Wang S, Kim K-M. The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol. International Journal of Molecular Sciences. 2024; 25(17):9644. https://doi.org/10.3390/ijms25179644

Chicago/Turabian Style

Kundu, Dooti, Xiao Min, Xiaohan Zhang, Xinru Tian, Shujie Wang, and Kyeong-Man Kim. 2024. "The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol" International Journal of Molecular Sciences 25, no. 17: 9644. https://doi.org/10.3390/ijms25179644

APA Style

Kundu, D., Min, X., Zhang, X., Tian, X., Wang, S., & Kim, K.-M. (2024). The Ubiquitination of Arrestin3 within the Nucleus Triggers the Nuclear Export of Mdm2, Which, in Turn, Mediates the Ubiquitination of GRK2 in the Cytosol. International Journal of Molecular Sciences, 25(17), 9644. https://doi.org/10.3390/ijms25179644

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