The proto-oncogene is a gene involved in cell proliferation in the cell and is essential for maintaining normal life activities of the body, and is highly conservative in evolution. When the structure or regulatory region of the proto-oncogene is mutated, and the gene product is increased or the activity is enhanced, the cells are excessively proliferated, thereby forming a tumor referred to as TSG.
The proto-oncogene is the normal gene of the cell, and its expression product is extremely important to the physiological function of the cell. Only when the proto-oncogene is structurally altered or overexpressed, it may cause cell carcinogenesis.
First, the characteristics of proto-oncogene expression:
l, the expression level of protooncogene in normal cells is generally low, and is regulated by growth: its expression has three main characteristics: 1 with differentiation phase specificity; 2 cell type specificity; 3 cell cycle specificity.
2, the expression of protooncogenes in tumor cells has two common and prominent features: 1 some proto-oncogenes have high levels of expression into over-expression; 2 proto-oncogene expression levels and order disorder, no longer have cell cycle Specificity.
3. Cell differentiation and proto-oncogene expression. During differentiation, the expression of proto-oncogenes related to differentiation is increased, while the expression of proto-oncogenes related to cell proliferation is inhibited.
Second, the structural changes of proto-oncogenes and their expression activation:
(A) point mutation C--ras: 12, 13, and 61 codon mutations, present in a variety of tumors. C-ras encoded protein (21kD, P21): RAS, a GTP-binding protein with GTPase activity, is an important signal transduction molecule.
(II) Chromosome translocation Chromosome translocation: a process of rearrangement of a part of a chromosome due to rupture and association with other chromosomes. Proto-oncogene activation due to chromosomal translocation:
1. A transgenic gene that forms a fusion gene with another gene due to translocation, produces a fusion protein with oncogenic activity, such as t(9:22), which fuses c-abl with bcr to produce a carcinogenic P210 protein.
2. Because of the translocation surface, the expression of proto-oncogene is out of control. For example, t (8:14) translocation makes c-myc expression out of control.
(3) gene amplification gene amplification (gene amplification) is the increase in gene copy number. Such as HL-60 and other leukemia cells, C-myc amplification 8-22 times. Other: c-erb B, c-net.
(4) LTR insertion. LTR is a long terminal repeat at both ends of the retroviral genome containing a strong promoter sequence.
Third, the function of the proto-oncogene product:
Most proteins encoded by proto-oncogenes are components of complex cellular signaling networks and play important roles in signal transduction pathways.
The proto-oncogene product can be used as:
1. Growth factors such as sis (PDGF-β), fgf family (int-2, csf-1, etc.)
2, growth factor receptor (plasma membrane): with tyrosine protein kinase activity, such as neu, ht, met, erbB, trk, fms, ros-1 and so on.
3. Non-receptor tyrosine protein kinase (plasma membrane/cytoplasm) such as src family: src, syn, fyn, abl, lck, ros, yes, fes, ret, etc.
4. Serine/threonine protein kinase (cytoplasm): such as raf, raf-1, mos, pim-1.
5, G protein (medial side of the plasma membrane), with GTP binding and GTPase activity, such as H-ras, K-ras, N-ras, and mel and ral in the ras family.
6. Nuclear DNA binding proteins (transcription factors) such as the myc family, the fos family, the Jun family, the ets family, rel, erb A (steroid hormone receptor).
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