2. Academic Validation
  3. Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling

Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling

  • Mol Oncol. 2023 Jan 12. doi: 10.1002/1878-0261.13374.
Max Petersen 1 2 3,  Anna Chorzalska 1 2,  Makayla Pardo 1 2,  Anaelena Rodriguez 1 2,  John Morgan 4,  Nagib Ahsan 5 6 7,  Ting Zhao 8,  Olin Liang 1 2 9,  Leszek Kotula 10 11 12,  Paul Bertone 1 2 9,  Philip A Gruppuso 13,  Patrycja M Dubielecka 1 2 3 9
Affiliations

Affiliations

  • 1 Department of Medicine, Alpert Medical School, Brown University, Providence, RI, USA.
  • 2 Division of Hematology/Oncology, Rhode, Island Hospital, Providence, RI, USA.
  • 3 Department of Pathology and Laboratory Medicine, Division of Biology and Medicine, Brown University.
  • 4 Flow Cytometry and Cell Sorting Core Facility, Roger Williams Medical Center, Providence, RI, USA.
  • 5 COBRE Center for Cancer Research Development, Proteomics Core Facility, Rhode, Island Hospital, Providence, RI, USA.
  • 6 Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA.
  • 7 Mass Spectrometry, Proteomics and Metabolomics Core Facility, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK, USA.
  • 8 Department of Surgery, at Rhode, Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA.
  • 9 Legorreta Cancer Center at, Brown University, Alpert Medical School, Brown University, Providence, RI, USA.
  • 10 Department of Urology, SUNY Upstate Medical University, 750 East Adams Str, Syracuse, NY, 13010, USA.
  • 11 Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Str, Syracuse, NY, 13010, USA.
  • 12 Upstate Cancer Center, SUNY Upstate Medical University, 750 East Adams Str, Syracuse, NY, 13010, USA.
  • 13 Division of Pediatric Endocrinology, at Rhode, Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA.
PMID: 36635880 DOI: 10.1002/1878-0261.13374
Abstract

Dysregulation of the adaptor protein Abelson interactor 1 (ABI1) is linked to malignant transformation. To interrogate the role of ABI1 in Cancer development, we mapped the ABI1 interactome using proximity-dependent labeling (PDL) with biotin followed by mass spectrometry. Using a novel PDL data filtering strategy, considering both peptide spectral matches and peak areas of detected Peptides, we identified 212 ABI1 proximal interactors. These included WAVE2 complex components such as CYFIP1, NCKAP1 or WASF1, confirming the known role of ABI1 in the regulation of actin-polymerization-dependent processes. We also identified proteins associated with the TAK1-IKK pathway, including TAK1, TAB2 and RIPK1, denoting a newly identified function of ABI1 in TAK1-NF-κB inflammatory signaling. Functional assays using TNFα-stimulated, ABI1-overexpressing or ABI1-deficient cells showed effects on TAK1-NF-kB pathway-dependent signaling to RIPK1, with ABI1-knockout cells being less susceptible to TNFα-induced, RIPK1-mediated, TAK1-dependent Apoptosis. In sum, our PDL-based strategy enabled mapping of the ABI1 proximal interactome, thus revealing a previously unknown role of this adaptor protein in TAK1/RIPK1-based regulation of cell death and survival.

Keywords

ABL interactor 1; NF-κB; RIPK1; TAK1; TurboID; proximity proteomics.

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