CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway.

Wei Gan,Tiegang Li,Hua Zhao,Kuijie Liu,Jiangsheng Huang

doi:10.18632/oncotarget.17794

Wei Gan, Tiegang Li + Show 3 more

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https://doi.org/10.18632/oncotarget.17794

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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.

Highlights

Colorectal cancer (CRC), one of the most fatal diseased all over the world, has caused enormous economic and spiritual losses to people; identifying reliable prognostic markers and personalized treatment regimen still remain important challenges [1]
We revealed that Cyclin-dependent kinase 1 (CDK1) and Inhibitor of apoptosis stimulating protein of p53 (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
Results showed that CDK1 mRNA and iASPP mRNA was highly expressed in CRC tissues, compared to the normal tissues, and higher expressed in tissues derived from patients in advanced stages (Figure 1A and 1B, stage I + II P < 0.05, stage III and IV P < 0.01.)

Summary

Introduction

Colorectal cancer (CRC), one of the most fatal diseased all over the world, has caused enormous economic and spiritual losses to people; identifying reliable prognostic markers and personalized treatment regimen still remain important challenges [1]. A high ratio of CDK1 expression of nuclear/cytoplasmic predicts a poorer prognosis in patients with CRC [4]. This inspired us to investigate the role of CDK1 in the regulation of CRC cell proliferation and clinical features in patients with CRC. CDKs expression changes in cells often result in abnormal proliferation, as well as dysfunction of related genes or proteins [6]. CDK1/cyclin B kinase complex, a major regulatory factor of the G2/M transition, has been regarded as a major regulator of promoting cell cycle transitions at late G2 and mitosis through substrates phosphorylation and activating reorganization of the nuclear envelope, spindle apparatus and actin cytoskeleton. In circumstance of cancers, dysfunction of cell cycle regulatory proteins occurs frequently

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