The body's immune cells and a variety of pathogens are in a war all the time. Probably the most daunting war is the fighting between immune cells and cancer cells. The formation, transfer and spreading of cancer cells are not resulted from one single factor or protein, instead it results from the combination of a lot of interrelated and cooperative proteins. In other words, our body's immune system is facing a team, which is united but having different individual roles.
These cancer cells are very cunning -- they will "camouflage" into normal cells in a certain period of time, therefore escaping from the body's immune system. When the quantity of cancer cells reaches a certain number, they begin to compete with normal cells for the "control" of the body.
The terrifying thing about cancer cells is not only the infinite proliferation, but also the formation of an immunosuppressive microenvironment during the process, in which the immune cells are suppressed by a variety of mechanisms. The formation of the immunosuppressive microenvironment is the interaction of each small group in a cancer cell. For example, the "well-known" co-suppression molecule PD-1 / PD-L1 is the one who inhibits immune cell activity and helps cancer cells escape in the human body. Does PD-1 / PD-L1 sound familiar? Actually I wrote an article previously titled "The Monologue of Anti-cancer Drug", which states what PD-1 / PD-L1 does in the human body. The most recent research has shown that PD-1/PD-L1 is not working alone, the expression of PD-L1 in tumor cells is closely related to Cdk5, and Cdk5 is expected to become a new target for cancer immunotherapy. What on earth is Cdk5? It seems Cdk5 will take over PD-1 / PD-L1 (After all, the peak of the market is up to 35 billion!).
The full name of Cdk5 is cyclin-dependent protein kinase 5. The Cdk5 gene is located on chromosome 7, specifically 7q36, and is a 3.95 kb DNA sequence. The molecular weight of Cdk5 protein is 33 kDa. Cdk5 is a serine / threonine protease that specifically phosphorylates the serine and threonine sites of its substrate protein when it binds to its activator. However, phosphorylation of the substrate protein amino acid sequence has certain requirements, namely, the adjacent downstream of serine / threonine (+1) must be proline, and prefers basic group (Lysine and arginine) in the +3 amino acid. Briefly speaking, the phosphorylation substrates of Cdk5 generally have a specific S / TPXK / R sequence[1].
As a special member of the cyclin-dependent protease family, Cdk5 is not involved in cell cycle regulation, but plays very important roles in neuronal migration, differentiation and synaptic development during the CNS development, as well as synaptic plasticity, neuronal survival and death in the mature CNS. These roles are regulated through the phosphorylation of cytoskeleton proteins, signal molecules, regulatory proteins and other substrates[2,3].
Recently, a study published in the journal Science has shown that Cdk5 plays a key role in tumor development by regulating the immune response in mice, and shown that there is a positive correlation between Cdk5 and tumor cell PD-L1 expression. This study indicates that blocking Cdk5 might be another way to inhibit PD-1. This study opens the door to molecular therapies targeting Cdk5[4].
Cancer cells and immune cells fight all the times. Once the immune cells compromise, it will put a deadly threat to the human body's health. This is the moment to test the wisdom of mankind. Drugs that block the inhibition of cancer cells on the immune system have greatly enhanced the human's power in fighting cancer cells, and eventually win the battle.
Cusabio, as a good partner of life science research, manufactures and provides some products related to Cdk5, PD1, and PDL1, to facilitate your research in this area, including recombinant proteins, antibodies, and Elisa kits.
Cdk5-related products:
1. Recombinant Human Cyclin-dependent kinase 5(CDK5) (Product code: CSB-YP005067HU)
2. Recombinant Mouse Cyclin-dependent-like kinase 5(Cdk5) (Product code: CSB-YP005067MO)
3. Recombinant Mouse Cyclin-dependent-like kinase 5(Cdk5) (Product code: CSB-YP005067MO)
4. Recombinant Xenopus laevis Cyclin-dependent kinase 5(cdk5) (Product code: CSB-YP005067XBE)
5. Recombinant Glossina morsitans morsitans Cyclin-dependent kinase 5 homolog(Cdk5) (Product code: CSB-YP649274GGM)
6. Rabbit anti-Human CDK5 Polyclonal antibody (Product code: CSB-PA005067LA01HU)
7. Rabbit anti-Caenorhabditis elegans cdk-5 Polyclonal antibody (Product code: CSB-PA565347XA01CXY)
8. Rabbit anti-Drosophila melanogaster (Fruit fly) Cdk5 Polyclonal antibody (Product code: CSB-PA151943XA01DLU)
9. CDK5 Monoclonal Antibody (Product code: CSB-MA190728)
PD-L1-related products:
1. Recombinant Human Programmed cell death 1 ligand 1(CD274) (Product code: CSB-YP878942HU1)
2. Recombinant Mouse Programmed cell death 1 ligand 1(Cd274) (Product code: CSB-YP880615MO)
3. Human Programmed Death Ligand-1(PD-L1/CD274) ELISA Kit (Product code: CSB-E13644h)
4. Mouse Programmed cell death 1 ligand 1(CD274) ELISA kit (Product code: CSB-EL004911MO)
5. Rabbit anti-Human CD274 Polyclonal antibody (Product code: CSB-PA878942ESR1HU)
6. PD-L1 Monoclonal Antibody (Product code: CSB-MA878942A0m)
PD-1-related products:
1. Human Programmed Death 1(PD-1)ELISA KIT (Product code: CSB-E13643h)
2. Mouse Programmed Death 1(PD-1)ELISA Kit (Product code: CSB-E13586m)
3. Rabbit anti-Human PDCD1 Polyclonal antibody (Product code: CSB-PA619964LA01HU)
Reference:
[1] Dhariwala FA, Rajadhyaksha MS. An unusual member of the Cdk family: Cdk5. Cell Mol Neurobiol 2008; 28 (3):351-369.
[2] Wang J, Liu S, Fu Y, Wang JH, Lu Y. Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors. Nat Neurosci 2003; 6 (10): 1039-1047.
[3]Gong X, Tang X, Wiedmann M, Wang X, Peng J, Zheng D,Blair LA, Marshall J, Mao Z. Cdk5-mediated inhibition of the protective effects of transcription factor MEF2 in neurotoxicity-induced apoptosis. Neuron 2003; 38 (1): 33-46.
[4] Dixon Dorand R, Joseph Nthale, Myers J T et al. Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity
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