BioID identifies novel c-MYC interacting partners in cultured cells and xenograft tumors
Abstract
The BioID proximity-based biotin labeling technique was recently developed for the characterization of protein-protein interaction networks [1]. To date, this method has been applied to a number of different polypeptides expressed in cultured cells. Here we report the adaptation of BioID to the identification of protein-protein interactions surrounding the c-MYC oncoprotein in human cells grown both under standard culture conditions and in mice as tumor xenografts. Notably, in vivo BioID yielded >100 high confidence MYC interacting proteins, including >30 known binding partners. Putative novel MYC interactors include components of the STAGA/KAT5 and SWI/SNF chromatin remodeling complexes, DNA repair and replication factors, general transcription and elongation factors, and transcriptional co-regulators such as the DNA helicase protein chromodomain 8 (CHD8). Providing additional confidence in these findings, ENCODE ChIP-seq datasets highlight significant coincident binding throughout the genome for the MYC interactors identified here, and we validate the previously unreported MYC-CHD8 interaction using both a yeast two hybrid analysis and the proximity-based ligation assay. In sum, we demonstrate that BioID can be utilized to identify bona fide interacting partners for a chromatin-associated protein in vivo. This technique will allow for a much improved understanding of protein-protein interactions in a previously inaccessible biological setting.Biological significance The c-MYC (MYC) oncogene is a transcription factor that plays important roles in cancer initiation and progression. MYC expression is deregulated in more than 50% of human cancers, but the role of this protein in normal cell biology and tumor progression is still not well understood, in part because identifying MYC-interacting proteins has been technically challenging: MYC-containing chromatin-associated complexes are difficult to isolate using traditional affinity purification methods, and the MYC protein is exceptionally labile, with a half-life of only ~30 min. Developing a new strategy to gain insight into MYC-containing protein complexes would thus mark a key advance in cancer research. The recently described BioID proximity-based labeling technique represents a promising new complementary approach for the characterization of protein-protein interactions (PPIs) in cultured cells. Here we report that BioID can also be used to characterize protein-protein interactions for a chromatin-associated protein in tumor xenografts, and present a comprehensive, high confidence in vivo MYC interactome. This article is part of a Special Issue entitled: Protein dynamics in health and disease. Guest Editors: Pierre Thibault and Anne-Claude Gingras.
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BioID has been used extensively in vitro to define interacting protein partners and proteins in subcellular compartments, but its application in vivo is limited.
“BioID has been used extensively in vitro [162–166] to define interacting protein partners and proteins in subcellular compartments, but its application in vivo is limited.”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [165]
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- Authors
- Dingar, D., Kalkat, M., Chan, P.-K., Srikumar, T., Bailey, S. D., Tu, W. B., Coyaud, E., Ponzielli, R., Kolyar, M., Jurisica, I., Huang, A., Lupien, M., Penn, L. Z., & Raught, B.
- Affiliations
- University Health Network (CA)
- University of Toronto (CA)
- Corresponding author
- Penn, Linda Z.
- Raught, Brian
- ORCID
- Venue
- Journal of Proteomics
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 118
- Pages
- 95-111
- ISSN
- 1874-3919 (ISSN-L)
- OpenAlex
- W2063807804
- Cited by
- 131
- References
- 60
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 2 · 2023: 10 · 2022: 11 · 2021: 19 · 2020: 16 · 2019: 12 · 2018: 8 · 2017: 15 · 2016: 9 · 2015: 12 · 2014: 1
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Proteomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Cancer Society Research Institute (701154, MOP130340)
- Canadian Institutes of Health Research (MOP275788)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Biotin and Related Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- c-Myc, protein-protein interaction, BioID, proximity labeling, tumor xenografts, CHD8, SWI/SNF chromatin remodeling, chromatin proteins, transcriptional coregulators, transcription elongation factor
- MeSH terms
- Lysine Acetyltransferase 5, Animals, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Humans, Male, Neoplasm Transplantation, Neoplasms, Experimental, Transcription Factors, Proto-Oncogene Proteins c-myc, Mice, SCID, Mice, Inbred NOD, Cell Line, Tumor, Mice, Histone Acetyltransferases, Heterografts
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