The DNA deaminase APOBEC3B interacts with the cell-cycle protein CDK4 and disrupts CDK4-mediated nuclear import of cyclin D1

Jennifer L. McCann, Madeline M. Klein, Evelyn M. Leland, Emily K. Law, William L Brown, Daniel J. Salamango, Reuben Harris

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Apolipoprotein B mRNA editing enzyme catalytic subunit-like protein 3B (APOBEC3B or A3B), as other APOBEC3 members, is a single-stranded (ss)DNA cytosine deaminase with antiviral activity. A3B is also overexpressed in multiple tumor types, such as carcinomas of the bladder, cervix, lung, head/neck, and breast. A3B generates both dispersed and clustered C-to-T and C-to-G mutations in intrinsically preferred trinucleotide motifs (TCA/TCG/TCT). A3B-catalyzed mutations are likely to promote tumor evolution and cancer progression and, as such, are associated with poor clinical outcomes. However, little is known about cellular processes that regulate A3B. Here, we used a proteomics approach involving affinity purification coupled to MS with human 293T cells to identify cellular proteins that interact with A3B. This approach revealed a specific interaction with cyclin-dependent kinase 4 (CDK4). We validated and mapped this interaction by co-immunoprecipitation experiments. Functional studies and immunofluorescence microscopy experiments in multiple cell lines revealed that A3B is not a substrate for CDK4–Cyclin D1 phosphorylation nor is its deaminase activity modulated. Instead, we found that A3B is capable of disrupting the CDK4-dependent nuclear import of Cyclin D1. We propose that this interaction May favor a more potent antiviral response and simultaneously facilitate cancer mutagenesis.

Original languageEnglish (US)
Pages (from-to)12099-12111
Number of pages13
JournalJournal of Biological Chemistry
Issue number32
StatePublished - Aug 9 2019

Bibliographical note

Funding Information:
This work was supported by the University of Minnesota Masonic Cancer Center, Academic Health Center, and College of Biological Sciences and in part by National Science Foundation Graduate Research Fellowship Grant 00039202 (to J. L. M.). The authors declare that they have no conflicts of interest with the contents of this article.

Publisher Copyright:
© 2019 McCann et al.


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