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From single cells to multicells: How does Cyclin D affect the process of life?
In the regulation of the cell cycle, Cyclin D is a key protein that plays an indispensable role in cell growth and proliferation. As a member of the Cyclin protein family, the synthesis of Cyclin D begins in the G1 phase and drives the G1/S phase transition, which is critical for cell development and the formation of multicellular organisms.
The protein structure length of Cyclin D ranges from 155 amino acids (as in the zebra shellworm) to 477 amino acids (as in the fruit fly).
Cells enter the cell cycle when they reach a certain size or in the presence of appropriate growth factors and nutrients. In multicellular organisms, the Cyclin-Cdk complex is an important factor in triggering various stages of the cell cycle. These Cyclins form the active form of the enzyme with Cyclin-dependent protein kinase (Cdk) and maintain its concentration by regulating the synthesis and degradation of Cyclin. Cyclin D is particularly important because it interacts with Cdk2, Cdk4, Cdk5 and Cdk6.
In proliferating cells, the accumulation of Cyclin D-Cdk4/6 complex is critical for cell cycle progression.
The function of Cyclin D and cell cycle
The main function of Cyclin D is to promote the G1/S transition, which is achieved through its partial phosphorylation of the retinoblastoma suppressor protein Rb. When Rb is phosphorylated, its ability to bind to E2F transcription factors is reduced, thereby promoting the expression of genes such as Cyclin E, which are particularly important for S phase progression.
Some studies have suggested that the amount of Cyclin D gradually increases during the G1 phase, which increases the activities of Cyclin D-Cdk4 and Cdk6. The stable expression of Cyclin D in the G1 phase is a key mechanism for cells to enter division. However, Cyclin D must form a complex with Cdk4 or Cdk6 to affect the G1/S transition.
The connection between cell proliferation and cancer
Because Cyclin D plays an important role in cell cycle regulation and growth factor signaling, it is also considered a potential oncogene. The occurrence of many human cancers is related to misregulation of the cell cycle, and overexpression of Cyclin D can shorten the duration of the G1 phase. Abnormal production of Cyclin D may lead to increased formation of the CDK4 complex, thereby preventing cells from passing the G1/S checkpoint in the absence of growth factors.
Overexpression of Cyclin D1 is sufficient to induce mammalian tumor formation, which is related to enhanced cell proliferation, improved cell survival rate and genetic instability.
Different cancer types have differences in the expression of Cyclin D. For example, Cyclin D gene amplification can be seen in bladder cancer and esophageal cancer, while other tumors such as colorectal cancer and melanoma may not show gene amplification. , but there is also overexpression of Cyclin D.
The regulatory mechanism of Cyclin D
The regulation of Cyclin D in vertebrates involves several pathways, including the Ras/MAP kinase and β-catenin-Tcf/LEF pathways. These pathways increase the expression of Cyclin D by activating the transcription factor Myc and so on. In some cases, DNA damage can rapidly trigger the degradation of Cyclin D, which can effectively inhibit excessive cell proliferation.
The observed importance of dysregulation of Cyclin D in relation to tumorigenesis suggests this protein as a potential therapeutic target for cancer.
In summary, Cyclin D not only plays a key role in the life cycle of single cells, but also plays an important role in the proliferation and differentiation of multicellular organisms. With a deeper understanding of the function of Cyclin D, scientists are working hard to explore its relationship with various diseases, especially cancer, and to seek potential treatment options in the future. So how should we adapt Cyclin D research to address the growing threat of cancer?
