Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling
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 fil...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-11-01
|
| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13374 |
| _version_ | 1797642592811220992 |
|---|---|
| author | Max Petersen Anna Chorzalska Makayla Pardo Anaelena Rodriguez John Morgan Nagib Ahsan Ting C. Zhao Olin Liang Leszek Kotula Paul Bertone Philip A. Gruppuso Patrycja M. Dubielecka |
| author_facet | Max Petersen Anna Chorzalska Makayla Pardo Anaelena Rodriguez John Morgan Nagib Ahsan Ting C. Zhao Olin Liang Leszek Kotula Paul Bertone Philip A. Gruppuso Patrycja M. Dubielecka |
| author_sort | Max Petersen |
| collection | DOAJ |
| description | 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 the 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. |
| first_indexed | 2024-03-11T14:02:44Z |
| format | Article |
| id | doaj.art-9feb2424ca384d45925ebb57c2e9eae4 |
| institution | Directory Open Access Journal |
| issn | 1574-7891 1878-0261 |
| language | English |
| last_indexed | 2024-03-11T14:02:44Z |
| publishDate | 2023-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj.art-9feb2424ca384d45925ebb57c2e9eae42023-11-02T04:03:00ZengWileyMolecular Oncology1574-78911878-02612023-11-0117112356237910.1002/1878-0261.13374Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signalingMax Petersen0Anna Chorzalska1Makayla Pardo2Anaelena Rodriguez3John Morgan4Nagib Ahsan5Ting C. Zhao6Olin Liang7Leszek Kotula8Paul Bertone9Philip A. Gruppuso10Patrycja M. Dubielecka11Department of Medicine, Alpert Medical School Brown University Providence RI USADepartment of Medicine, Alpert Medical School Brown University Providence RI USADepartment of Medicine, Alpert Medical School Brown University Providence RI USADepartment of Medicine, Alpert Medical School Brown University Providence RI USAFlow Cytometry and Cell Sorting Core Facility Roger Williams Medical Center Providence RI USACOBRE Center for Cancer Research Development, Proteomics Core Facility Rhode Island Hospital Providence RI USADepartment of Surgery Rhode Island Hospital and Warren Alpert Medical School of Brown University Providence RI USADepartment of Medicine, Alpert Medical School Brown University Providence RI USADepartment of Urology SUNY Upstate Medical University Syracuse NY USADepartment of Medicine, Alpert Medical School Brown University Providence RI USADivision of Pediatric Endocrinology Rhode Island Hospital and Warren Alpert Medical School of Brown University Providence RI USADepartment of Medicine, Alpert Medical School Brown University Providence RI USADysregulation 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 the 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.https://doi.org/10.1002/1878-0261.13374ABL interactor 1NF‐κBproximity proteomicsRIPK1TAK1TurboID |
| spellingShingle | Max Petersen Anna Chorzalska Makayla Pardo Anaelena Rodriguez John Morgan Nagib Ahsan Ting C. Zhao Olin Liang Leszek Kotula Paul Bertone Philip A. Gruppuso Patrycja M. Dubielecka Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling Molecular Oncology ABL interactor 1 NF‐κB proximity proteomics RIPK1 TAK1 TurboID |
| title | Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling |
| title_full | Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling |
| title_fullStr | Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling |
| title_full_unstemmed | Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling |
| title_short | Proximity proteomics reveals role of Abelson interactor 1 in the regulation of TAK1/RIPK1 signaling |
| title_sort | proximity proteomics reveals role of abelson interactor 1 in the regulation of tak1 ripk1 signaling |
| topic | ABL interactor 1 NF‐κB proximity proteomics RIPK1 TAK1 TurboID |
| url | https://doi.org/10.1002/1878-0261.13374 |
| work_keys_str_mv | AT maxpetersen proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT annachorzalska proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT makaylapardo proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT anaelenarodriguez proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT johnmorgan proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT nagibahsan proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT tingczhao proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT olinliang proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT leszekkotula proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT paulbertone proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT philipagruppuso proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling AT patrycjamdubielecka proximityproteomicsrevealsroleofabelsoninteractor1intheregulationoftak1ripk1signaling |