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Protein Interaction Map of APOBEC3 Enzyme Family Reveals Deamination-Independent Role in Cellular Function
Gwendolyn M Jang1, Arun Kumar Annan Sudarsan2, Arzhang Shayeganmehr2
1Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, California, USA; Quantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, California, USA; J. David Gladstone Institutes, Gladstone Institute for Data Science and Biotechnology, San Francisco, California, USA.
Molecular & Cellular Proteomics : MCP
|March 28, 2024
Summary
Human APOBEC3 enzymes, crucial for innate immunity, interact with RNA and proteins. Misregulation links APOBEC3s to cancer, with new interactions found in RNA biology and tumor suppression.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Human APOBEC3 enzymes are cytidine deaminases critical for intrinsic immunity against viruses.
- They function by deaminating cytosine, inactivating viral genomes, and possess deamination-independent antiviral activities.
- Misregulated APOBEC3 expression can lead to genomic instability and contribute to cancer development.
Purpose of the Study:
- To elucidate the protein interaction network of human APOBEC3 enzymes.
- To understand the role of RNA in APOBEC3 interactions and functions.
- To investigate potential links between APOBEC3 interactions and cancer biology.
Main Methods:
- Affinity purification mass spectrometry (AP-MS) was employed to identify protein interactions.
- Protein-protein and protein-RNA mediated interactions were mapped for APOBEC3 family members.
- Functional assays assessed the impact of APOBEC3B interaction with prefoldin 5 (PFD5) on c-Myc degradation.
Main Results:
- Novel RNA-mediated interactions were identified between APOBEC3C, APOBEC3G, and APOBEC3H with spliceosome proteins, and tRNA methylation/ncRNA export factors.
- RNA-independent interactions were found between APOBEC3B, APOBEC3D, APOBEC3F, and the prefoldin family.
- APOBEC3B interaction with PFD5 inhibited PFD5's ability to degrade the oncogene c-Myc.
Conclusions:
- APOBEC3 enzymes engage in diverse RNA-mediated and RNA-independent interactions, revealing novel roles in RNA biology.
- Non-redundant protein-protein interactions, including with tumor suppressors, suggest a significant role for APOBEC3s in cancer biology.
- The identified interactions provide new avenues for understanding APOBEC3 functions and their implications in disease.
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