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CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway
Wei Gan1, Hua Zhao1, Tiegang Li1
1Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha 410011, Hunan, China.
Abstract:
CDK1 (cyclin-dependent kinase 1) is a critical regulator of the G2-M checkpoint. CDK1 is considered a possible target for cancer treatment. In addition to CDK1, iASPP plays essential role in maintaining cancer cell proliferation. In the present study, we monitored the expression of CDK1 and iASPP at mRNA and protein levels in CRC tissues and cell lines; we also predicted that iASPP protein might interact with CDK1 protein. By performing GST pull-down assay and Co-IP assay, we confirmed the interaction of CDK1 and iASPP protein. In CRC cell lines, CDK1 interacted with iASPP to affect CRC cell proliferation and apoptosis; moreover, the p53 apoptosis pathway was involved in this progression. Taken together, we revealed that CDK1 and iASPP was up-regulated in CRC tissues and cell lines; CDK1 protein interacted with iASPP protein to affect CRC cell proliferation and apoptosis through the p53 apoptosis pathway. CDK1 and iASPP might serve as not only promising targets in CRC treatment, but also efficient prognostic markers. From the perspective of protein interactions, we provided a novel theoretical basis for targeted therapy of CRC.
Insights
Cyclin-dependent kinase 1 (CDK1) and iASPP are upregulated in colorectal cancer (CRC) and promote cancer cell proliferation. Their interaction affects CRC cell apoptosis via the p53 pathway, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cyclin-dependent kinase 1 (CDK1) regulates the G2-M checkpoint and is a potential cancer therapeutic target.
- Inhibition of Interacting SH3 Domain Protein (iASPP) is crucial for controlling cancer cell proliferation.
Purpose of the Study:
- To investigate the expression of CDK1 and iASPP in colorectal cancer (CRC).
- To determine the interaction between CDK1 and iASPP proteins.
- To elucidate the role of CDK1-iASPP interaction in CRC cell proliferation and apoptosis via the p53 pathway.
Main Methods:
- Monitoring mRNA and protein expression of CDK1 and iASPP in CRC tissues and cell lines.
- GST pull-down and Co-immunoprecipitation (Co-IP) assays to confirm protein interaction.
- Analysis of the p53 apoptosis pathway in CRC cell lines.
Main Results:
- CDK1 and iASPP were found to be upregulated in CRC tissues and cell lines.
- Direct interaction between CDK1 and iASPP proteins was confirmed.
- The CDK1-iASPP interaction was shown to influence CRC cell proliferation and apoptosis, involving the p53 pathway.
Conclusions:
- CDK1 and iASPP are upregulated in CRC and interact to affect cell proliferation and apoptosis through the p53 pathway.
- CDK1 and iASPP represent promising therapeutic targets and prognostic markers for CRC.
- This study provides a novel theoretical basis for targeted CRC therapy based on protein interactions.
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