Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling.
Max PetersenAnna ChorzalskaMakayla PardoAnaelena RodriguezJohn MorganNagib AhsanTing ZhaoOlin LiangLeszek KotulaPaul BertonePhilip A GruppusoPatrycja M DubieleckaPublished in: Molecular oncology (2023)
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.
Keyphrases
- label free
- cell cycle arrest
- cell death
- induced apoptosis
- mass spectrometry
- oxidative stress
- signaling pathway
- rheumatoid arthritis
- pi k akt
- squamous cell carcinoma
- computed tomography
- cell proliferation
- optical coherence tomography
- immune response
- nuclear factor
- young adults
- electronic health record
- amino acid
- machine learning
- big data
- diabetic rats
- high glucose
- high throughput
- toll like receptor
- inflammatory response
- liquid chromatography
- artificial intelligence
- endothelial cells
- lymph node metastasis