title: TPPII, MYBBP1A and CDK2 form a protein-protein interaction network.
abstract: Tripeptidyl-peptidase II (TPPII) is an aminopeptidase with suggested regulatory effects on cell cycle, apoptosis and senescence. A protein-protein interaction study revealed that TPPII physically interacts with the tumor suppressor MYBBP1A and the cell cycle regulator protein CDK2. Mutual protein-protein interaction was detected between MYBBP1A and CDK2 as well. In situ Proximity Ligation Assay (PLA) using HEK293 cells overexpressing TPPII forming highly enzymatically active oligomeric complexes showed that the cytoplasmic interaction frequency of TPPII with MYBBP1A increased with the protein expression of TPPII and using serum-free cell growth conditions. A specific reversible inhibitor of TPPII, butabindide, suppressed the cytoplasmic interactions of TPPII and MYBBP1A both in control HEK293 and the cells overexpressing murine TPPII. The interaction of MYBBP1A with CDK2 was confirmed by in situ PLA in two different mammalian cell lines. Functional link between TPPII and MYBBP1A has been verified by gene expression study during anoikis, where overexpression of TPP II decreased mRNA expression level of MYBBP1A at the cell detachment conditions. All three interacting proteins TPPII, MYBBP1A and CDK2 have been previously implicated in the research for development of tumor-suppressing agents. This is the first report presenting mutual protein-protein interaction network of these proteins.
authors.affiliation: Uppsala University, Department of Medical Biochemistry and Microbiology (IMBIM), BMC, Box 582, SE-751 23 Uppsala, Sweden. Electronic address: jarmila.nahalkova@imbim.uu.se.
authors.forename: Jarmila
authors.initials: J
authors.lastname: Nahálková
authors.affiliation: Uppsala University, Department of Medical Biochemistry and Microbiology (IMBIM), BMC, Box 582, SE-751 23 Uppsala, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Tomkinson
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D023102:Anoikis / Q000187:drug effects / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D020014:K562 Cells; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D029543:Nucleocytoplasmic Transport Proteins / Q000096:biosynthesis* / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*; D016601:RNA-Binding Proteins; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D007211:Indoles; C491719:MYBBP1A protein, human; D009687:Nuclear Proteins; D029543:Nucleocytoplasmic Transport Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C098807:butabindide; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases
keywords: Apoptosis; CDK2; Cell cycle; MYBBP1A; TPPII