Drug Target and Biomarker: Comprehensive Summary of CDKN2A (G1029)

Target Name: CDKN2A

NCBI ID: G1029

CDKN2A

Drug Target and Biomarker: Comprehensive Summary of CDKN2A

CDKN2A plays a crucial role in preventing senescence entry. Targeting CDKN2A with a specific mutation prevents senescence and increases the proliferative capacity of cells.

The transcriptional factors Smads, DMP1alpha, E2Fs, MYC, and FoxO activate ARF transcription, while E2F3b, Ezh2/Twist-1, CBX7, TBX2, BMI-1, and EGFR suppress ARF transcription. TGFbeta1 negatively regulates ARF transcription.

ARF function, stability, and localization are regulated by phosphorylation, ubiquitination, protein-protein interactions (PPIs), and chaperone-mediated autophagy (CMA). Various proteins, including PKCalpha, MKRN1, Siva1, ULF1, USP10, PANO, NPM, TBP-1, REG-gamma, and MDM2, regulate ARF through these mechanisms.

The CD47/NF-kB pathway plays a role in regulating UHRF1 and p16INK4A expression. CD47 activation induces the translocation of the active NF-kB complex, leading to UHRF1 gene activation and p16INK4A repression, promoting cell proliferation. Blocking CD47 function inhibits NF-kB transactivation, resulting in decreased cell proliferation via p16INK4A reactivation.

In carcinoids, CDK4/6 complex and CCND1 drive cell cycle progression, while in carcinomas, CDKN2A is upregulated, resulting in downregulation of these cell cycle mediators. Carcinomas instead rely on CDK2 and CCNE1 for cell cycle progression. Carcinomas also exhibit elevated expression of the anti-apoptotic protein BCL2, leading to apoptosis insensitivity.

Please note that the viewpoints have been summarized and merged from the provided context information without using any prior knowledge.
Based on the provided context, we can summarize some key viewpoints regarding the effect of p19 on the level of DCL1 and AGO2 during Cymbidium ringspot virus (CymRSV) infection:

Effect of p19 on the level of DCL1:
- In the presence of p19, the expression of DCL1 is increased during CymRSV infection through the high-affinity binding of NbmiR162.
- This increased expression of DCL1 leads to an elevation in the expression of miRNAs, including miR168, which may act provirally.
- High levels of DCL1 suggestedly downregulate DCL4 expression, while the levels of DCL2 remain unaffected.
- The p19 protein not only enhances miR168-mediated restriction of AGO1 expression by inducing miR168 accumulation but also reduces the association of miR168 with its target.
- In the absence of p19, miR162 downregulates the expression of DCL1, resulting in low levels of miRNA expression and higher levels of DCL4.

Effect of p19 on the level of AGO2:
- p19 increases the expression of AGO2 by binding to NbmiR403 during CymRSV infection.
- However, in the absence of p19, the level of AGO2 remains unaffected.

In summary, p19 plays a significant role in modulating the levels of DCL1 and AGO2 during CymRSV infection. It enhances the expression of DCL1, leading to increased miRNA expression, while also promoting miR168-mediated restriction of AGO1 expression. Additionally, p19 increases the expression of AGO2. These findings provide insights into the intricate interactions between viral proteins and host factors during CymRSV infection.

Protein Name: Cyclin Dependent Kinase Inhibitor 2A

Functions: Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein

The "CDKN2A Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about CDKN2A comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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