Cell cycle related kinase (CCRK) is a newly discovered protein recognition kinase, also known as p42 or CDK (cyclin-dependent kinase) related protein kinase PNQLARE (genBank TMAAF89089), with a molecular weight of about 42kD. The position on the chromosome is 9q22.1, the genome is 8 kb in length, and there are 7 exons whose sequence is homologous to Cdk-activating Kinase 1p (Cak1p) and human CDK7. CCRK is homologous to Cdk1, 2 and 7, and to a lesser extent homologous to Csk.4,5. CCRK has been reported to activate Cdk2 and support cell proliferation, and was found to phosphorylate male germ cell-associated kinase (MAK) -related kinases.
CCRK promoter research
The CCRK coding gene was first found to be highly expressed in human malignant glioma tissue, but its function is unknown. Scientists studied the characteristics of the CCRK promoter and identified the transcription initiation point of the human CCRK gene by using 5'-RACE technology. Double luciferase was used to analyze the upstream site and electrophoretic migration and other experimental methods. The human CCRK promoter, the core sequence of the promoter, and transcription factors related to its expression were explored. 441/367) region, and found that there are three important binding sites in this region: Delta EF1, NF-κB and Sp1, of which Delta EF1 and NF-κB transcription factors are related to human CCRK expression. In addition, Farcas et al studied the methylation and expression of CCRK in the cerebral cortex of primates and found that the phosphorylation level of the CpG region of CCRK coding genes in adult cerebral cortex is higher than that of chimpanzees. A species-specifically methylated region (SMR) is located between the fully methylated 5 'end and the fully demethylated 3' end of the putative CCRKCGI promoter. Some Alu-Sg1 repeats in humans and New World monkeys are integrated into the CCRK promoter region, and the mRNA expression of CCRK also changes with the evolution process. It can be inferred that CCRK plays an important role in the evolution of primate brains, and it plays a major role in the initiation of CCRK transcription. The above research has laid the foundation for future research on CCRK transcriptional regulation mechanism, and provided new ideas for the research on the mechanism of various cancers.
CCRK research in different cancer tissues
In the cell cycle, the corresponding cyclin and CDK are assembled into a full enzyme, and the phosphorylation of cyclin dependent kinase-activating kinase (CAK) is required to promote the conversion of cells from G1 to S phase. Promote cell proliferation. Kaldis and other researchers believe that CCRK can be used as a CAK to promote the conversion of the corresponding protein into the cell cycle, thereby promoting cell proliferation. According to the subcellular localization of CCRK in the nucleus and the surrounding nucleus, it is known that CCRK is generally relatively high expressed in the cytoplasm. In human tissues, CCRK is mainly expressed in the brain and kidney, but less in the liver, heart, and placenta. In recent years, various studies in vivo and in vitro found that CCRK is widely overexpressed in various cancer cells, such as: malignant glioma cells (U373, U87), cervical cancer cells (HeLa), osteosarcoma cells (U2OS), and colorectal cancer cells (HCT116). ), Ovarian cancer cells (UACC1598, TOV21G, HO8910, OVCAR3, YACC326), liver cancer cells (SK-Hep1), etc. It can be inferred that the expression change of CCRK in the body is closely related to the occurrence and development of various cancer tissues, and can be used as an independent factor to predict the cell proliferation of certain cancer tissues. At the same time, CCRK is considered as a potential CAK and oncoprotein.
Conclusions
CCRK is a new CAK. The high expression of CCRK is closely related to the invasion and metastasis of the corresponding cancer cells and the survival rate of cancer patients. During different cell carcinogenesis, it exerts its unique regulatory role through corresponding signal pathways, especially for cyclinD1, The regulation of pCDK2-cyclinE and β-catenin / TCF signaling pathways is closely related to cancer cell proliferation. Therefore, in tumor drug research, it may be considered to interfere with the corresponding targets of these signals in order to reduce the proliferation of cancer cells.
References: