ArticlePLoS pathogens2013
Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
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- Emerging Mechanisms of GmBio · 2021Review
- CVB3 VP1 interacts with MAT1 to inhibit cell proliferation by interfering with Cdk-activating kinase complex activity in CVB3-induced acute pancreatitis.PLoS pathogens · 2021Article
- Cross-regulation of viral kinases with cyclin A secures shutoff of host DNA synthesis.Nature communications · 2020Article
- Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules.Frontiers in microbiology · 2020Review
- Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via pUL97.Nature microbiology · 2019Article
- SAMHD1 Modulates Early Steps during Human Cytomegalovirus Infection by Limiting NF-κB Activation.Cell reports · 2019Article
- Coxsackievirus A6 Induces Cell Cycle Arrest in G0/G1 Phase for Viral Production.Frontiers in cellular and infection microbiology · 2018Article
- Human cytomegalovirus miR-US5-1 inhibits viral replication by targeting Geminin mRNA.Virologica Sinica · 2017Article
- Synthetic lethal mutations in the cyclin A interface of human cytomegalovirus.PLoS pathogens · 2017Article
- Article
- Human cytomegalovirus riding the cell cycle.Medical microbiology and immunology · 2015Review
- Enterovirus 71 mediates cell cycle arrest in S phase through non-structural protein 3D.Cell cycle (Georgetown, Tex.) · 2015Article
- PUL21a-Cyclin A2 interaction is required to protect human cytomegalovirus-infected cells from the deleterious consequences of mitotic entry.PLoS pathogens · 2014Article
- Functional annotation of human cytomegalovirus gene products: an update.Frontiers in microbiology · 2014Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cyclin A is critical for cellular DNA synthesis and S phase progression of the cell cycle. Human cytomegalovirus (HCMV) can reduce cyclin A levels and block cellular DNA synthesis, and cyclin A overexpression can repress HCMV replication. This interaction has only been previously observed in HCMV as murine CMV does not downregulate cyclin A, and the responsible viral factor has not been identified. We previously reported that the HCMV protein pUL21a disrupted the anaphase-promoting complex (APC), but a point mutant abrogating this activity did not phenocopy a UL21a-deficient virus, suggesting that pUL21a has an additional function. Here we identified a conserved arginine-x-leucine (RxL) cyclin-binding domain within pUL21a, which allowed pUL21a to interact with cyclin A and target it for proteasome degradation. Homologous pUL21a proteins from both chimpanzee and rhesus CMVs also contained the RxL domain and similarly degraded cyclin A, indicating that this function is conserved in primate CMVs. The RxL point mutation disabled the virus' ability to block cellular DNA synthesis and resulted in a growth defect similar to pUL21a-deficient virus. Importantly, knockdown of cyclin A rescued growth of UL21a-deficient virus. Together, these data show that during evolution, the pUL21a family proteins of primate CMVs have acquired a cyclin-binding domain that targets cyclin A for degradation, thus neutralizing its restriction on virus replication. Finally, the combined proteasome-dependent degradation of pUL21a and its cellular targets suggests that pUL21a may act as a novel suicide protein, targeting its protein cargos for destruction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.