Cyclin-dependent kinase

Cyclin-dependent kinase
Identifiers
EC no.2.7.11.22
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
KEGGKEGG entry
MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
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NCBIproteins
Tertiary structure of human Cdk2, determined by X-ray crystallography. Like other protein kinases, Cdk2 is composed of two lobes: a smaller amino-terminal lobe (top) that is composed primarily of beta sheet and the PSTAIRE helix, and a large carboxy-terminal lobe (bottom) that is primarily made up of alpha helices. The ATP substrate is shown as a ball-and-stick model, located deep within the active-site cleft between the two lobes. The phosphates are oriented outward, toward the mouth of the cleft, which is blocked in this structure by the T-loop (highlighted in green). (PDB 1hck)

Cyclin-dependent kinases (CDKs) are a predominant group of serine/threonine protein kinases involved in the regulation of the cell cycle and its progression, ensuring the integrity and functionality of cellular machinery. These regulatory enzymes play a crucial role in the regulation of eukaryotic cell cycle and transcription, as well as DNA repair, metabolism, and epigenetic regulation, in response to several extracellular and intracellular signals.[1][2] They are present in all known eukaryotes, and their regulatory function in the cell cycle has been evolutionarily conserved.[3][4] The catalytic activities of CDKs are regulated by interactions with CDK inhibitors (CKIs) and regulatory subunits known as cyclins. Cyclins have no enzymatic activity themselves, but they become active once they bind to CDKs. Without cyclin, CDK is less active than in the cyclin-CDK heterodimer complex.[5][6] CDKs phosphorylate proteins on serine (S) or threonine (T) residues. The specificity of CDKs for their substrates is defined by the S/T-P-X-K/R sequence, where S/T is the phosphorylation site, P is proline, X is any amino acid, and the sequence ends with lysine (K) or arginine (R). This motif ensures CDKs accurately target and modify proteins, crucial for regulating cell cycle and other functions.[7] Deregulation of the CDK activity is linked to various pathologies, including cancer, neurodegenerative diseases, and stroke.[6]

  1. ^ Ding L, Cao J, Lin W, Chen H, Xiong X, Ao H, et al. (March 2020). "The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer". International Journal of Molecular Sciences. 21 (6): 1960. doi:10.3390/ijms21061960. PMC 7139603. PMID 32183020.
  2. ^ Hives M, Jurecekova J, Holeckova KH, Kliment J, Sivonova MK (2023). "The driving power of the cell cycle: cyclin-dependent kinases, cyclins and their inhibitors". Bratislavske Lekarske Listy. 124 (4): 261–266. doi:10.4149/BLL_2023_039. PMID 36598318.
  3. ^ S GB, Gohil DS, Roy Choudhury S (January 2023). "Genome-wide identification, evolutionary and expression analysis of the cyclin-dependent kinase gene family in peanut". BMC Plant Biology. 23 (1): 43. doi:10.1186/s12870-023-04045-w. PMC 9850575. PMID 36658501.
  4. ^ Morgan D (2007). The Cell Cycle: Principles of Control. London: New Science Press Ltd. pp. 2–54, 196–266. ISBN 978-0-9539181-2-6.
  5. ^ Alberts B, Hopkin K, Johnson A, Morgan D, Raff M, Roberts K, Walter P (2019). Essential Cell Biology (5th ed.). W. W. Norton & Company. pp. 613–627. ISBN 9780393679533.
  6. ^ a b Łukasik P, Załuski M, Gutowska I (March 2021). "Cyclin-Dependent Kinases (CDK) and Their Role in Diseases Development-Review". International Journal of Molecular Sciences. 22 (6): 2935. doi:10.3390/ijms22062935. PMC 7998717. PMID 33805800.
  7. ^ Malumbres M (June 30, 2014). "Cyclin-dependent kinases". Genome Biology. 15 (6): 122. doi:10.1186/gb4184. PMC 4097832. PMID 25180339.