1. Academic Validation
  2. Mapping Proximity Associations of Core Spindle Assembly Checkpoint Proteins

Mapping Proximity Associations of Core Spindle Assembly Checkpoint Proteins

  • J Proteome Res. 2021 Jul 2;20(7):3414-3427. doi: 10.1021/acs.jproteome.0c00941.
Yenni A Garcia 1 Erick F Velasquez 1 Lucy W Gao 2 Ankur A Gholkar 1 Kevin M Clutario 1 Keith Cheung 1 Taylor Williams-Hamilton 1 Julian P Whitelegge 2 3 4 Jorge Z Torres 1 3 4
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
  • 2 Pasarow Mass Spectrometry Laboratory, The Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California 90095, United States.
  • 3 Molecular Biology Institute, University of California, Los Angeles, California 90095, United States.
  • 4 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, California 90095, United States.
Abstract

The spindle assembly checkpoint (SAC) is critical for sensing defective microtubule-kinetochore attachments and tension across the kinetochore and functions to arrest cells in prometaphase to allow time to repair any errors before proceeding into anaphase. Dysregulation of the SAC leads to chromosome segregation errors that have been linked to human diseases like Cancer. Although much has been learned about the composition of the SAC and the factors that regulate its activity, the proximity associations of core SAC components have not been explored in a systematic manner. Here, we have taken a BioID2-proximity-labeling proteomic approach to define the proximity protein environment for each of the five core SAC proteins BUB1, BUB3, BUBR1, MAD1L1, and MAD2L1 in mitotic-enriched populations of cells where the SAC is active. These five protein association maps were integrated to generate a SAC proximity protein network that contains multiple layers of information related to core SAC protein complexes, protein-protein interactions, and proximity associations. Our analysis validated many known SAC complexes and protein-protein interactions. Additionally, it uncovered new protein associations, including the ELYS-MAD1L1 interaction that we have validated, which lend insight into the functioning of core SAC proteins and highlight future areas of investigation to better understand the SAC.

Keywords

BioID2; cell division; protein associations; protein networks; proximity labeling; spindle assembly checkpoint (SAC).

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