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AnyGenes

G2-M REGULATORS: KEY PLAYERS IN CELL CYCLE CONTROL

G2-M regulators are essential for controlling the transition between the G2 phase and M phase of the cell cycle, ensuring proper cell division. This critical checkpoint allows the cell to repair DNA damage and prepare for mitosis, maintaining genomic stability.

AnyGenes offers advanced qPCR arrays that allow for the high-throughput analysis of G2-M regulators across various species. These customizable tools enable researchers to gain deeper insights into cell cycle regulation and its implication in cancer, providing reliable solutions for both basic and clinical research.

AnyGenes G2-M Regulators SignArray® for Advanced Cell Cycle Analysis
Activation of the G2/M checkpoint after DNA damage

Activation of the G2/M checkpoint after DNA damage. In response to DNA damage, the ATM, ATR signaling pathway is activated, which leads to the phosphorylation and activation of Chk1 and Chk2 and to the subsequent phosphorylation of Cdc25. Phosphorylated Cdc25 is sequestered in the cytoplasm by 14-3-3 proteins, which prevents activation of cyclinB/Cdk1 by Cdc25 and results in G2 arrest. Activated ATM/ATR also activates p53-dependent signaling. This contributes to the maintenance of G2 arrest by upregulating 14-3-3, which sequesters Cdk1 in the cytoplasm. In addition, p53 induces the transactivation of p21, a Cdk inhibitor that binds to and inhibits cyclinB/Cdk1 complexes. P: phosphorylation.

KEY COMPONENTS

The G2/M checkpoint is a crucial regulatory mechanism in the cell cycle that ensures cells do not enter mitosis with damaged or incompletely replicated DNA. Here are the key components involved in this regulation:

  • Cyclin-Dependent Kinases (CDKs): such as Cdc2/Cdk1 andCyclin B.
  • Negative regulators: such as p21, p27,Wee1 and Myt1.
  • Checkpoint kinases: such as Chk1, Chk2 and ATM/ATR.
  • Tumor suppressor proteins: such as p53.
  • Anaphase Promoting Complex/Cyclosome (APC/C).
  • Centrosome-Associated Regulators.
  • Surviving and heat-shock proteins: such as Survivin, Heat-shock protein 90 (Hsp90).

KEY FUNCTIONS of G2-M REGULATORS

  • DNA damage response: The G2/M checkpoint prevents cells with damaged DNA from proceeding to mitosis, allowing time for repair mechanisms to function.
  • Regulatory Proteins: including Cyclin-dependent kinases (CDKs), particularly Cdc2 (Cdk1) and cyclin B, which drive the transition into mitosis. Checkpoint Kinases (ATM, ATR, Chk1/2, and Wee1), and Tumor Suppressors such as p53.
  • Centrosome Function: Recent studies highlight the centrosome's role as a hub for G2/M checkpoint regulation.

ROLE OF G2-M REGULATORS IN DNA DAMAGE REPAIR

G2-M regulators play a crucial role in ensuring that cells do not enter mitosis with damaged DNA. At the G2-M checkpoint, cells assess DNA integrity and activate repair mechanisms if necessary. The G2-M transition is controlled by regulators like ATM/ATR and Chk1/Chk2 kinases, which respond to DNA damage by halting the cell cycle, allowing time for repair before mitosis begins.

CLINICAL IMPLICATIONS

The dysregulation of G2/M checkpoints is often observed in various cancers, making these regulators potential targets for therapeutic interventions. For instance:

  • Targeting CDKs: Inhibitors of CDKs have shown promise in enhancing the sensitivity of cancer cells to chemotherapy and radiotherapy by disrupting their cell cycle control mechanisms.
  • Biomarkers for Prognosis: Certain genes associated with the G2/M checkpoint have been identified as potential biomarkers for cancer prognosis, particularly in hepatocellular carcinoma (HCC) where high expression correlates with poor outcomes.
(1) Sugiyama H, et al. Live-cell imaging defines a threshold in CDK activity at the G2/M transition. Dev Cell. (2024)26;59(4):545-557.e4.
(2) Barnaba N, & LaRocque JR. Targeting cell cycle regulation via the G2-M checkpoint for synthetic lethality in melanoma. Cell Cycle. (2021);20(11):1041-1051.
(3) Thae Hnit SS, et al. Transcriptional regulation of G2/M regulatory proteins and perturbation of G2/M Cell cycle transition by a traditional Chinese medicine recipe. J Ethnopharmacol.(2020)6:251:112526.
(4) Yin L, et al. G2/M checkpoint plays a vital role at the early stage of HCC by analysis of key pathways and genes. Oncotarget. (2017)18;8(44):76305–76317.
(4) Wang Y, et al. Centrosome-associated regulators of the G2/M checkpoint as targets for cancer therapy. Mol Cancer. (2009)13;8:8.

G2-M REGULATORS BIOMARKER LIST

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to get started on your project.

You can check the biomarker list included in this pathway, see below: