Drug Target and Biomarker: CDKN1A (G1026)

NCBI ID: G1026

CDKN1A

Drug Target and Biomarker: CDKN1A

Four E3 ligases, namely SCFSKP2, APC/CCDC20, CRL4CDT2, and CRL2LRR1, are involved in p21 ubiquitylation and degradation. While the first three ligases regulate p21 in the nucleus during cell-cycle regulation, CRL2LRR1 targets p21 in the cytoplasm to control cell migration.
Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a role in regulating the expression of CDKN1A. Some ncRNAs inhibit CDKN1A transcription, leading to p21 repression, while others enhance CDKN1A transcription, resulting in increased levels of p21.
FXR1 mediates the stabilization of miR301a-3p, which protects p21 from degradation by a 3'-5' exonuclease. In cancer cells with depleted FXR1, miR301a-3p is degraded, leading to p21 stabilization and upregulation.
Newborn CD4+ T cells have a distinct pathway of IFN-beta signaling, where exposure to IFN-beta does not induce the cell cycle inhibitor p21, unlike in adult CD4+ T cells. This difference in p21 induction influences the inhibitory effect of IFN-beta on newborn CD4+ T cells in terms of proliferation, phosphorylation of Rb, and cytokine production.
HDAC1 and HDAC6 regulate the expression of RhoB, which, in turn, can induce either apoptosis/cell death or cytostasis. The induction of p21 by RhoB leads to cytostasis and no combinatorial synergy.

Based on the provided context information, several key viewpoints and findings related to CDKN1A (also known as p21) can be identified:

In osteosarcoma, the lncRNA Lnc-KASRT interacts with SRSF1 and regulates alternative splicing of KLF6, leading to increased growth and invasion of cancer cells. This regulation modifies the P21/CCND1 pathway.

The "friction model" suggests that the balance between survival and apoptosis in response to DNA damage is determined by the interplay between p53 (driving force) and p21 (friction force).

Nobiletin, when combined with palbociclib, shows synergistic anti-tumor activity by downregulating SKP2 levels, leading to the accumulation of p21 and p27. This inhibits G1-phase-related protein CDK2 and inhibits cell proliferation in renal carcinoma cell lines.

Wounded p21-deficient animals exhibit diminished Sdf1 induction and recruitment of Cxcr4+ leukocytes, allowing for lineage-restricted tissue regeneration.

In advanced colon cancer, both TGFbeta and activin signaling pathways upregulate p21, but in a ligand-specific manner. Activin induces downregulation of p21 via PI3K/Akt signaling. Nuclear p21 expression may serve as a functional surrogate for intact TGFbeta/SMAD growth suppression, while loss of nuclear p21 suggests potential benefit from activin, TGFbeta, or combination inhibitory therapy.

These findings highlight the involvement of CDKN1A (p21) in various cellular processes and its role in different disease contexts.

Protein Name: Cyclin Dependent Kinase Inhibitor 1A

Functions: May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657)

The "CDKN1A 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 CDKN1A comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
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•   the target screening and validation;
•   expression level;
•   disease relevance;
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•   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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