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 ATM
Signaling Pathway
The
ataxia telangiectasia-mutated gene (ATM)
encodes a protein kinase that acts as a tumor
suppressor.
ATM activation by ionizing radiation
damage to DNA stimulates DNA repair and blocks
progression through the cell cycle. |
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cdc25
and chk1 Regulatory Pathway in response to DNA
damage
Cdc25 is a protein phosphatase responsible for dephosphorylating and activating cdc2, a crucial step in regulating the entry of all eukaryotic cells into the M-phase of the cell cycle. Cdc25 is phosphorylated throughout interphase but not in mitosis.
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Cell Cycle Regulation and Cyclins
The cell cycle is regulated by the interplay of many molecules. Key among these are the cyclins which are expressed and then degraded in a concerted fashion to drive the stages of the cell cycle. Cyclins combine with cyclin dependent kinases (cdks) to form activated kinases that phosphorylate targets leading to cell cycle regulation. A breakdown in the regulation of this cycle can lead to out of control growth and contribute to tumor formation. Defects in many of the molecules that regulate the cell cycle have been implicated in cancer. Key among these are p53, the cdk inhibitors (p15, p16, p18, p19, p21, p27), and Rb, all of which act to keep the cell cycle from progressing until all repairs to damaged DNA have been completed. |
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Cell
Cycle: G1/S Check Point
The
G1/S cell cycle checkpoint controls the
passage of eukaryotic cells from the first
‘gap’ phase (G1) into the DNA synthesis
phase (S). Two cell cycle kinases,
CDK4/6-cyclin D and CDK2-cyclin E, and the
transcription complex that includes Rb and E2F
are pivotal in controlling this checkpoint.
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Cell
Cycle: G2/M Checkpoint
The
G2/M DNA damage checkpoint prevents the cell
from entering mitosis (M phase) if the genome
is damaged. The Cdc2-cyclin B kinase is
pivotal in regulating this transition. During
G2 phase, Cdc2 is maintained in an inactive
state by the kinases Wee1 and Myt1.
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p53
Signaling Pathway
p53 is a transcription factor who's activity is regulated by phosphorylation. The function is p53 is to keep the cell from progressing through the cell cycle if there is damage to DNA present. It may do this in multiple ways from holding the cell at a checkpoint until repairs can be made to causing the cell to enter apoptosis if the damage cannot be repaired. The critical role of p53 is evidenced by the fact that it is mutated in a very large fraction of tumors from nearly all sources. |
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RB
Tumor Suppressor/Checkpoint Signaling in
response to DNA damage
Cell cycle checkpoint controls at the G1 to S transition and the G2 to M transition prevent the cell cycle from progressing when DNA is damaged. The ATM protein kinase detects DNA damage and in response to this activates DNA repair factors and inhibits cell cycle progression. |
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Rgt1
in Yeast Glucose Induction Pathway
Yeast sense glucose in their environment and alter gene expression to match their nutritional needs. In a glucose-rich environment, glycolysis is activated, glucose transport is increased and gluconeogenesis repressed to use glucose to make energy. |
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Snf1
in Yeast Glucsoe Repression/Derepression Pathway
The Snf1 protein kinase is a central component of the
signaling pathway for glucose repression in yeast. On removal of glucose, gene repression is relieved via a mechanism that requires the pophorylation of Mig1 protein repressor by Snf1 protein kinase complex. |
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Stress
Related Signaling Pathway |
