Cell Cycle pathway

 

The cell cycle pathway is a unidirectional process that governs cell division. This process, which cannot be reversed once started, is critical for cell survival. The cell cycle typically involves four phases: S phase, in which DNA is replicated, M phase, in which chromosomes are separated and two distinct cells are formed, and G1 and G2 phases during which the cell is preparing for cell division. The majority of the cell cycle pathway is regulated by two classes of proteins: cyclin-dependent kinases (CDKs) and cyclins. Cyclins and CDKs form complexes that enable CDKs to phosphorylate and activate specific cell cycle intermediates. In the initial stages of the cell-cycle signal, cyclin D will bind to CDK4 and this complex will phosphorylate the retinoblastoma (Rb) gene[1]. During a quiescent state, Rb is bound to DNA and blocks the transcription of specific genes. After phosphorylation, Rb becomes unbound and genes necessary for the cell cycle are now accessible.

The cell cycle pathway is a highly-regulated process that incorporates three major checkpoints. The first checkpoint is the G1 checkpoint, which determines whether or not a cell will enter into the cell division process. The second checkpoint, G2, will determine if the cell will enter into mitosis. Both the G1 and G2 checkpoints can be affected by the presence or absence of various growth factors, DNA damage, or replicative senescence. The final checkpoint, metaphase, ensures proper chromosome alignment prior to cell division. The cell cycle pathway is intrinsically linked to cell survival and cell death. For instance, failure of a cell to meet the requirements of the individual cell cycle checkpoints will result in the cell undergoing apoptosis.

In cancer, the cell cycle checkpoints are often dysfunctional. Checkpoint proteins, such as Rb or p53, are often mutated or inactivated and this can result in cell division despite incomplete DNA synthesis and segregation errors. Inappropriate continuation of the cell cycle can lead to genomic instability, which is a common feature of malignant cells.

1. Nigg. 1995. Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle. Bioessays. 17(6):471-80.

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Cell Cycle pathway image by Aviva Systems Biology

RB1 CHEK1 CHEK2 SKP1 CUL1 RBX1 GADD45G GADD45A GADD45B YWHAQ YWHAB YWHAE YWHAG YWHAH YWHAZ RB1 SKP1 CUL1 RBX1 PCNA ANAPC10 CDC26 ANAPC13 ANAPC2 ANAPC4 ANAPC5 ANAPC7 ANAPC11 ANAPC1 CDC23 CDC16 CDC27 SMC1B SMC1A PTTG2 PTTG1 ANAPC10 CDC26 ANAPC13 ANAPC2 ANAPC4 ANAPC5 ANAPC7 ANAPC11 ANAPC1 CDC23 CDC16 CDC27 CDC20 FZR1 PLK1 CDC25A CDC25B CDC25C CCNA2 CCNA1 CCNB3 CCNB1 CCNB2 ORC6 ORC3 ORC1 ORC4 RB1 MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 MAD2L2 MAD2L1 YWHAQ YWHAB YWHAE YWHAG YWHAH YWHAZ CCNH CDK7 CCNA2 CCNA1 CDK2 CCND1 CCND2 CCND3 CDK4 CDK6 CDK2 CCNE1 CCNE2 E2F1 E2F2 E2F3 TFDP1 TFDP2 RBL1 RBL2 CREBBP EP300 CDKN2D CDKN1B CDKN1C SMAD2 SMAD3 SMAD4 GSK3B TGFB1 TGFB2 TGFB3 MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 MDM2 DNA-PK ATM ATR ESP1 CIP1 CDK1 CDK1 HDAC ORC P53 BUB1 ARF

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