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Cell Division Cycle

All organisms (single and multi-cellular) rely upon reiteration of growth and division of existing cells under favorable conditions. During each round of this process, the cell cycles through an ordered series of events in which its genetic information is duplicated and then divided among two daughter cells. These events are tightly regulated and certain checkpoints must be passed in order for the cell cycle to be completed. The loss of control of these processes is a hallmark of cancer.

The cell cycle is split up into four major phases based on the events unfolding in the cell. During the first gap phase (G1) the proteins are produced that are essential for DNA replication. The genetic information is then being replicated during the synthesis (S) phase. In the second gap phase (G2) all the components that are necessary for the separation of the duplicated DNA during the subsequent mitosis (M phase). Cells that are not actively dividing are considered to be in a quiescent state in the resting phase G0.

Cell division is necessary for life, but unregulated division is dangerous and counterproductive. Therefore, the cell has an impetus for maintaining tight regulatory control over how and when division takes place. There are two major checkpoints in the cell cycle. The first choke-point the cell must pass is between the G1 and S phase. A second opportunity for arrest is provided between G2 and M phases. Once DNA replication has been initiated, it must be finished. Therefore, the major checkpoint in the cell cycle is the restriction (R) point between G1 and S phases, prior to DNA duplication, at which the cycle progresses depending on mitogenic or inhibitory factors such as DNA damage and signals from various signaling pathways.

Progression from one phase to another is controlled by cyclin dependent kinases (CDK) and their activators, cyclins. Latter proteins are unstable and their cellular concentration cycles throughout the cell cycle. Accordingly, specific cyclin-CDK complexes persist in an active form for a very short period of time after translation, and are then degraded or inactivated by the time that particular phase of the cell cycle completes. Activation of specific cyclin-CDK complexes are characteristic for the different cell cycle phases, and drive production of specific molecules associated with, and necessary for that phase of division. Additional levels of dynamic control are also provided by CDK inhibitors, which block CDK function even in the presence of their requisite cyclin.

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Cyclin Dependent Kinase

CDK1 (Cyclin-Dependent Kinase 1):

The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is a catalytic subunit of the highly conserved protein kinase complex known as M-phase promoting factor (MPF), which is essential for G1/S and G2/M phase transitions of eukaryotic cell cycle. Mitotic cyclins stably associate with this protein and function as regulatory subunits. The kinase activity...   More...

CDK2 (Cyclin-Dependent Kinase 2):

The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein kinase is highly similar to the gene products of S. cerevisiae cdc28, and S. pombe cdc2. It is a catalytic subunit of the cyclin-dependent protein kinase complex, whose activity is restricted to the G1-S phase, and essential for cell cycle G1/S phase transition. This protein associates with and...   More...

Cyclins

CCNB1 - Cyclin B1

The protein encoded by this gene is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). Two alternative transcripts have been found, a constitutively expressed transcript and a cell cycle-regulated transcript, that is expressed predominantly during G2/M phase. The different transcripts result from the use of...   More...

CCNE1 - Cyclin E1

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex...   More...

G1-S Checkpoint

CDC25A (Cell Division Cycle 25 Homolog A (S. Pombe)):

CDC25A is a member of the CDC25 family of phosphatases. CDC25A is required for progression from G1 to the S phase of the cell cycle. It activates the cyclin-dependent kinase CDC2 by removing two phosphate groups. CDC25A is specifically degraded in response to DNA damage, which prevents cells with chromosomal abnormalities from progressing through cell division. CDC25A is an oncogene, although...   More...

CDKN2B (Cyclin-Dependent Kinase Inhibitor 2B (p15, Inhibits CDK4)):

MNAT1 (Menage A Trois Homolog 1, Cyclin H Assembly Factor (Xenopus Laevis)):

RASGRF1 (Ras Protein-Specific Guanine Nucleotide-Releasing Factor 1):

CDKN2C (Cyclin-Dependent Kinase Inhibitor 2C (p18, Inhibits CDK4)):

CDKN2D (Cyclin-Dependent Kinase Inhibitor 2D (p19, Inhibits CDK4)):

E2F/RB

RB1 - Retinoblastoma 1

The protein encoded by this gene is a negative regulator of the cell cycle and was the first tumor suppressor gene found. The encoded protein also stabilizes constitutive heterochromatin to maintain the overall chromatin structure. The active, hypophosphorylated form of the protein binds transcription factor E2F1. Defects in this gene are a cause of childhood cancer retinoblastoma (RB), bladder...   More...

E2F1 (E2F Transcription Factor 1):

The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a...   More...

E2F4 (E2F Transcription Factor 4, P107/p130-Binding):

G2-M Checkpoint

MNAT1 (Menage A Trois Homolog 1, Cyclin H Assembly Factor (Xenopus Laevis)):

RASGRF1 (Ras Protein-Specific Guanine Nucleotide-Releasing Factor 1):

PLK1 (Polo-Like Kinase 1):

PPM1D (Protein Phosphatase, Mg2+/Mn2+ Dependent, 1D):

GADD45B (Growth Arrest and DNA-Damage-Inducible, beta):

M Phase

INCENP (Inner Centromere Protein Antigens 135/155kDa):

In mammalian cells, 2 broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger,' or transiently interacting, proteins (reviewed by Choo, 1997). The constitutive proteins include CENPA (centromere protein A\; MIM 117139), CENPB (MIM 117140), CENPC1 (MIM 117141), and CENPD (MIM 117142). The term 'passenger proteins' encompasses...   More...

EPR1 (Early-Phytochrome-Responsive1):

CSN Complex

COPS6 (COP9 Constitutive Photomorphogenic Homolog Subunit 6 (Arabidopsis)):

COPS2 - COP9 Constitutive Photomorphogenic Homolog Subunit 2 (Arabidopsis):

COPS3 (COP9 Constitutive Photomorphogenic Homolog Subunit 3 (Arabidopsis)):

COPS4 (COP9 Constitutive Photomorphogenic Homolog Subunit 4 (Arabidopsis)):

COPS5 (COP9 Constitutive Photomorphogenic Homolog Subunit 5 (Arabidopsis)):

COPS7A (COP9 Constitutive Photomorphogenic Homolog Subunit 7A (Arabidopsis)):

COPS7B (COP9 Constitutive Photomorphogenic Homolog Subunit 7B (Arabidopsis)):

COPS8 (COP9 Constitutive Photomorphogenic Homolog Subunit 8 (Arabidopsis)):

SCF Complex

CUL1 - Cullin 1

Core component of multiple cullin-RING-based SCF (SKP1- CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the...   More...

RBX1 (Ring-Box 1, E3 Ubiquitin Protein Ligase):

DREAM complex

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