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Updated: Apr 22, 2026

Probing High-density Functional Protein Microarrays to Detect Protein-protein Interactions
Published on: August 2, 2015
TPPII, MYBBP1A and CDK2 form a protein-protein interaction network
Jarmila Nahálková1, Birgitta Tomkinson1
1Uppsala University, Department of Medical Biochemistry and Microbiology (IMBIM), BMC, Box 582, SE-751 23 Uppsala, Sweden.
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.
Insights
Tripeptidyl-peptidase II (TPPII) interacts with MYBBP1A and CDK2, revealing a novel protein network. This discovery offers new insights into cell cycle regulation and potential tumor suppressor development.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Tripeptidyl-peptidase II (TPPII) is an aminopeptidase implicated in cell cycle regulation, apoptosis, and senescence.
- MYBBP1A acts as a tumor suppressor, and CDK2 is a key cell cycle regulator.
- Previous research suggested roles for these proteins in cancer, but their interactions were not fully understood.
Purpose of the Study:
- To investigate the protein-protein interactions between TPPII, MYBBP1A, and CDK2.
- To elucidate the functional relationship between TPPII and MYBBP1A in cellular processes.
- To establish a novel protein-protein interaction network involving these three key proteins.
Main Methods:
- Protein-protein interaction studies.
- In situ Proximity Ligation Assay (PLA) in HEK293 and other mammalian cell lines.
- Gene expression analysis during anoikis.
- Inhibition studies using a specific TPPII inhibitor (butabindide).
Main Results:
- TPPII was found to physically interact with both MYBBP1A and CDK2.
- MYBBP1A and CDK2 also exhibit mutual protein-protein interactions.
- TPPII-MYBBP1A cytoplasmic interactions increased with TPPII expression and were suppressed by butabindide.
- Overexpression of TPPII decreased MYBBP1A mRNA levels during anoikis.
- This study presents the first report of a mutual protein-protein interaction network for TPPII, MYBBP1A, and CDK2.
Conclusions:
- A novel protein interaction network involving TPPII, MYBBP1A, and CDK2 has been identified.
- These interactions are modulated by TPPII expression levels and activity.
- The findings provide a foundation for understanding the roles of these proteins in cell cycle control and tumor suppression.
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