A healthy immune system requires a series of checkpoints to ensure self tolerance and prevent damage to other tissues during immune response. Binding of costimulatory signal transduction molecules (such as CD28, ICOS, GITR) on T cells to their receptors (such as CD80/CD86, ICOSL, GITRL) on antigen presenting cells (APCs) may contribute to T cell activation. However, in some states, inhibitory signals of T cell activation and response occur during the involvement of T cell receptors. These signals are generated by proteins involved in immune checkpoints (eg, PD-1, CTLA-4, TIM-3, and LAG3). Usually PD-1 and CTLA-4 immunological checkpoint proteins are upregulated in T cells infiltrating tumors and bind to their respective ligands, PD-L1 (ligand B7-H1)/PD-L2 (ligand B7- DC) and CD80/86, and down-regulate T cell responses. Immunological checkpoint ligands are often upregulated in cancer cells as a means of evading immune detection. Therefore, immunotherapy by blocking immunological checkpoint protein activation of anti-tumor immunity has become a popular research subject for cancer therapy.
The G2/M cycle checkpoint prevents cells with genomic DNA damages from entering mitosis (M phase). The Cyclin B-CDK1 complex plays an important regulatory role during the G2 transition, at which time CDK1 is maintained inactivated by the tyrosine kinases Wee1 and Myt1. When the cells enter the M phase, the kinase Aurora A and the cofactor Bora act together to activate PLK1, which in turn activates the activity of phosphatase CDC25 and downstream CDC2, effectively driving the cells into mitosis. When the DNA is damaged, it activates the DNA-PK/ATM/ATR kinase and eventually inactivates the Cyclin B-CDK1 complex.
The G1/S cell cycle checkpoints control whether eukaryotic cells enter the S phase (synthesis phase) of DNA synthesis through the G1 phase. Two cell cycle kinase complexes, CDK4/6-Cyclin D and CDK2- Cyclin E, work together to relieve the inhibition of dynamic transcriptional complexes containing retinoblastoma protein (Rb) and E2F. In cells undefined during the G1 phase, hypophosphorylated Rb binds to the E2F-DP1 transcription factor and forms an inhibitory complex with HDAC, thereby inhibiting downstream key transcriptional activities. Clear entry into the S phase is achieved by continuous phosphorylation of Rb by Cyclin D-CDK4/6 and Cyclin E-CDK2, which separates the transcription factor E2F from the inhibitory complex and allows transcription of the gene required for DNA replication. After the growth factor disappears, the expression level of cylin D is down-regulated by down-regulation of protein expression and phosphorylation-dependent degradation.
Embryonic stem cells (ES cells) are pluripotent stem cells isolated from an inner cell mass of early-stage embryo-blastocysts. ES cells have a high differentiation potential. At the same time, while ES cells are undifferentiated, they have the potential to infinitely replicate, making them highly attractive subjects for cell therapy and regenerative medicine.
CD molecules are cell surface markers that appear or disappear when cells (leukocytes, red blood cells, platelets, and vascular endothelial cells, etc.) differentiate or become different lineages, different segments of cells, become active or diseased. Most CD molecules are transmembrane proteins or glycoproteins, including extracellular regions, transmembrane regions, and cytoplasmic regions. Some CD molecules are "anchored" on the cell membrane by means of inositol phospholipids. A few CD molecules are carbohydrate haptens. The study of CD molecules can be used in many basic immunology research fields, such as the relationship between CD antigen structure and function, cell activation pathway, signal transduction and cell differentiation, etc. It can be used clinically for disease mechanism research, clinical diagnosis, disease prognosis, efficacy tracking and treatment, and more.
The Hippo signal is very conservative in evolution. It regulates organ size and tissue stability by regulating cell proliferation, apoptosis, and stem cell renewal. The core process of Hippo signaling is a kinase tandem process, Mst1/2 and Sav1 form a complex, phosphorylate and activate Lats1/2; Lats1/2 kinase then phosphorylates and inhibits transcriptional coactivators Yap and Taz. Yap and Taz are the most important effectors downstream of the Hippo pathway. Upon dephosphorylation, Yap and Taz translocate to the nucleus and interact with TEAD1-4 or other transcription factors (such as CTGF) to induce gene expression, thereby initiating cell proliferation and inhibiting apoptosis.