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

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.

In emergency departments, radiologists' access to EHRs may influence interpretations and medical management.

The adoption of electronic health records (EHRs) that meet federal meaningful-use standards is a major US national policy priority. Policy makers recognize the potential of electronic communication in delivering high-quality health care, particularly in an environment of expanding remote access to medical care and the ever-increasing need to transmit health care records across institutions. To demonstrate this principle, we sought to estimate the significance of EHR access in emergent neuroradiologic interpretations. Three neuroradiologists conducted a prospective expert-rater analysis of 2,000 consecutive head computed tomography (CT) exams ordered by emergency department (ED) physicians. For each head CT exam, the neuroradiologists compared medical information generated by ED physicians to information generated by the interpreting radiologists who had access to additional EHR-derived patient data. In 6.1 percent of the head CT exams, the neuroradiologists reached consensus--meaning two out of three agreed--that the additional clinical data derived from the EHR was "very likely" to influence radiological interpretations and that the lack of that data would have adversely affected medical management in those patients. Health care providers must recognize the value of implementing EHRs and foster their widespread adoption.