Protein phosphorylation is a reversible and dynamic post-translational modification that is governed by the opposing activities of phosphatases and kinases. Protein phosphatase enzymes remove phosphate groups that have been covalently attached to serine, threonine, and tyrosine residues by protein kinase enzymes. Alternatively, lipid phosphatases such as PTEN remove phosphate groups from lipid substrates. By counteracting the activities of kinases, phosphatases play an important role in the control of a wide variety of cellular functions including cell cycle checkpoints, responsiveness to growth factors, contact inhibition, and cellular motility. The phosphatases are associated with the Akt signaling pathway, which regulates cell growth, survival, proliferation, autophagy, and metabolism, such as CD45, CD45RO, and CDC25A.
Figure 1. Structure of the CDC25A protein. Based on PyMOL rendering of PDB 1c25.
CDC25A is a member of the CDC25A family of dual-specificity phosphatases. Dual specificity protein phosphatases remove phosphate groups from phosphorylated tyrosine and serine / threonine residues. They represent a subgroup of the tyrosine phosphatase family (as opposed to the serine/threonine phosphatase family). All mammals examined to date have three homologs of the ancestral Cdc25 gene (found e.g. in the fungus species S. pombe, designated CDC25A, Cdc25B, and Cdc25C. In contrast, some invertebrates harbour 2 (e.g., the Drosophila proteins String and Twine) or four (e.g., C. elegans Cdc-25.1 - Cdc-25.4) homologues. CDC25A is required for progression from the G1 phase to the S phase of the cell cycle, but also in late cell cycle events It works. In particular, it degenerates in metaphase cells and exits in the medium term, similar to cyclin B.It is competent to activate the G1/S cyclin-dependent kinases CDK4 and CDK2 by removing inhibitory phosphate groups from adjacent tyrosine and threonine residues; it can also activate Cdc2 (Cdk1), the principal mitotic Cdk.
Involvement in cancer
CDC25A is specifically degraded in response to DNA damage, resulting in cell cycle arrest. Thus, this degradation represents an axis of the DNA damage checkpoint, complementing the induction of p53 and p21 in CDK inhibition. CDC25A is considered to be an oncogene because it can cooperate with oncogenic RAS to transform rodent fibroblasts, and it is overexpressed in tumors from a variety of tissues, including breast and head and neck tumors. It is a target for the E2F transcription factor family. Therefore, its overexpression is a common consequence of the p53-p21-Cdk axis imbalance in carcinogenesis.
The CD45 molecule is expressed on all white blood cells and is called leukocyte common antigen (LCA). CD45 consists of a class of structurally similar, larger molecular weight transmembrane proteins that are widely present on the surface of leukocytes. The cytoplasmic segment has a protein tyrosine phosphatase that dephosphorylates tyrosine on substrates P56lck and P59fyn. Activation, which plays an important role in the signal transduction of cells, is a key molecule in signal transduction on the cell membrane. It plays an important role in lymphocyte development, function regulation and signal transmission. The distribution of CD45 can be used as some T cell sub- Group of classification signs.
The CD45 molecule is expressed on all white blood cells and is called the leukocyte common antigen. CD45 is a key molecule in signal transduction on the cell membrane and plays an important role in lymphocyte development, function regulation and signal transmission. It has been found that CD45 has at least 9 subtypes (such as cD45RA, cD45RB, cD45Rc, cD45R0, etc.), which are selectively linked by three different exons (A, B and C), which lack three exons. The subtype is called CD45R0, and the subtype expressing only exon A is called CD45RA.
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2. Zhao H.; et al. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc. Natl. Acad. Sci. U.S.A. 2002,99 (23): 14795-800.