CDK regulators—Cell cycle progression or apoptosis—Scenarios in normal cells and cancerous cells

• Published in: Advances in protein chemistry and structural biology Vol. 135; pp. 125 - 177
• Main Authors: Nilmani, D'costa, Maria, Bothe, Anusha, Das, Soumik, Udhaya Kumar, S., Gnanasambandan, R., George Priya Doss, C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 2023
• Subjects: Apoptosis; CDKs; Cell Cycle; Cell Cycle Proteins - genetics; CKIs; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - pharmacology; Cyclin-Dependent Kinases; Humans; Pan-CDK inhibitors; Ribosomal protein inhibiting CDKs; Therapeutics; CDKs; Cell cycle; Therapeutics; Pan-CDK inhibitors; Ribosomal protein inhibiting CDKs; CKIs; Apoptosis
• ISSN: 1876-1623; 1876-1631; 1876-1631
• DOI: 10.1016/bs.apcsb.2022.11.008

Serine/threonine kinases called cyclin-dependent kinases (CDKs) interact with cyclins and CDK inhibitors (CKIs) to control the catalytic activity. CDKs are essential controllers of RNA transcription and cell cycle advancement. The ubiquitous overactivity of the cell cycle CDKs is caused by a number of genetic and epigenetic processes in human cancer, and their suppression can result in both cell cycle arrest and apoptosis. This review focused on CDKs, describing their kinase activity, their role in phosphorylation inhibition, and CDK inhibitory proteins (CIP/KIP, INK 4, RPIC). We next compared the role of different CDKs, mainly p21, p27, p57, p16, p15, p18, and p19, in the cell cycle and apoptosis in cancer cells with respect to normal cells. The current work also draws attention to the use of CDKIs as therapeutics, overcoming the pharmacokinetic barriers of pan-CDK inhibitors, analyze new chemical classes that are effective at attacking the CDKs that control the cell cycle (cdk4/6 or cdk2). It also discusses CDKI's drawbacks and its combination therapy against cancer patients. These findings collectively demonstrate the complexity of cancer cell cycles and the need for targeted therapeutic intervention. In order to slow the progression of the disease or enhance clinical outcomes, new medicines may be discovered by researching the relationship between cell death and cell proliferation.