CDK5: A Potential Drug Target and Biomarker for Cancer Treatment

Target Name: CDK5

NCBI ID: G1020

CDK5

CDK5: A Potential Drug Target and Biomarker for Cancer Treatment

Cancer is a leading cause of morbidity and mortality worldwide, affecting millions of individuals worldwide. The rapid growth of cancer cells has resulted in a need for effective cancer treatments that can inhibit the uncontrolled cell division associated with cancer. One of the key targets for cancer treatment is the cell division protein kinase (CDK), which is involved in regulating cell division. CDK5, a key subunit of the CDK4 complex, has been identified as a potential drug target and biomarker for cancer treatment.

CDK5: Structure and Function

CDK5 is a 21-kDa protein that is expressed in various tissues, including liver, pancreas, and gastrointestinal tract. It is a key component of the CDK4 complex, which is involved in regulating cell growth and division. The CDK4 complex consists of the following subunits: CDK4, CDK6, p21 (CDK inhibitor), and p53 ( tumor suppressor), while CDK5 is the protein that catalyzes the kinetic activity of the complex.

CDK5 plays a crucial role in cell growth and division by regulating the activity of several transcription factors, including PTEN, p21, and p53. It has been shown that CDK5 activation is associated with cancer cell proliferation and survival.

CDK5 as a Potential Drug Target

CDK5 has been identified as a potential drug target for cancer treatment due to its involvement in cell division and the development of cancer. Several studies have shown that inhibition of CDK5 activity can lead to a reduction in cancer cell proliferation and survival.

One of the main advantages of targeting CDK5 is its potential for targeting a wide range of cancer types, as many CDK5-positive tumors have been shown to have poor prognosis. Additionally, CDK5 inhibition has been shown to be effective in preclinical models of cancer treatment, including in models of breast, lung, and ovarian cancer.

CDK5 as a Biomarker

CDK5 has also been identified as a potential biomarker for cancer diagnosis and treatment. The expression of CDK5 has been shown to be elevated in various types of cancer, including breast, ovarian, and prostate cancer. Additionally, some studies have shown that CDK5 expression is associated with poor prognosis in cancer patients.

CDK5 has also been used as a biomarker for evaluating the efficacy of cancer treatments. For instance, some studies have shown that the expression of CDK5 is reduced in response to chemotherapy, which could be used as a biomarker for the effectiveness of chemotherapy in cancer treatment.

CDK5 inhibition has also been shown to be associated with improved outcomes in patients with advanced cancer, including increased overall survival and reduced disease recurrence.

Conclusion

CDK5 is a protein that plays a crucial role in cell division and has been identified as a potential drug target for cancer treatment. Its inhibition has been shown to be effective in preclinical models of cancer treatment and can be used as a biomarker for cancer diagnosis and treatment. Further studies are needed to confirm its potential as a drug target and biomarker for cancer treatment.

Protein Name: Cyclin Dependent Kinase 5

Functions: Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Negatively regulates the CACNA1B/CAV2.2 -mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in postmitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-BMAL1 heterodimer in association with altered stability and subcellular distribution

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•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
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•   related combination drugs;
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