Quantitative Proteomics of the SMAD (Suppressor of Mothers against Decapentaplegic) Transcription Factor Family Identifies Importin 5 as a Bone Morphogenic Protein Receptor SMAD-specific Importin.

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Mutations in the GSTFs Suppressor of Mothers Against Decapentaplegic 2 (SMAD2) and SMAD4 are frequently associated with colon and rectal carcinomas. These proteins play an important role in bone morphogenic protein (BMP) and transforming growth factor β (TGF-β) signaling pathways controlling cell fate and proliferation. To study the protein interactome of the SMAD protein family we generated a quantitative proteomics pipeline that allows for inducible expression of GFP-tagged SMAD proteins followed by affinity purification and quantitative mass spectrometry analysis. Data are available via ProteomeXchange with identifier PXD004529. The nuclear importin IPO5 was identified as a novel interacting protein of SMAD1. Overexpression of IPO5 in various cell lines specifically increases nuclear localization of BMP receptor-activated SMADs (R-SMADs) confirming a functional relationship between IPO5 and BMP but not TGF-β R-SMADs. Finally, we provide evidence that variation in length of the lysine stretch of the nuclear localization sequence is a determinant for importin specificity.", "claims": [{"id": "claim-target-result", "statement": "No numerical result for the registered target is stated; the paper reports a quantitative proteomics pipeline involving quantitative mass spectrometry analysis, with source data available via ProteomeXchange under identifier PXD004529, and its headline biological finding is that IPO5 was identified as a novel interacting protein of SMAD1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27703004", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "To study the protein interactome of the SMAD protein family we generated a quantitative proteomics pipeline that allows for inducible expression of GFP-tagged SMAD proteins followed by affinity purification and quantitative mass spectrometry analysis."}, {"asset": "source:pmid:27703004", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Data are available via ProteomeXchange with identifier PXD004529."}, {"asset": "source:pmid:27703004", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The nuclear importin IPO5 was identified as a novel interacting protein of SMAD1."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "No numerical result for the registered target is stated; the paper reports a quantitative proteomics pipeline involving quantitative mass spectrometry analysis, with source data available via ProteomeXchange under identifier PXD004529, and its headline biological finding is that IPO5 was identified as a novel interacting protein of SMAD1.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:27703004"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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