[Research advances on p53 gene network].
The p53 tumor suppressor gene integrates numerous signals to control cell life and death. p53 and its function-related genes consists of a complicated gene network. When a highly connected node in the network breaks down, the disruption of p53 has severe consequences. p53 gene locates in human chromosome 17q13.1. Its encoding wild-type p53 protein is composed of four parts: N-terminal activation domain, DNA-binding domain, oligomerization domain, and C-terminal regulation domain. As the gene structures of p73, p51, p63 are similar with p53, they are regarded as members of p53 gene family. p53 play an intermediate role connecting varied stress signals with the reactions of cells. DNA damage caused by ionizing radiation, aberrant growth signals, or chemotherapeutic drugs may activate the p53 network. When expression of p53 elevated, p53-mdm2 and p14(ARF)-mdm2 feedback loops can accurately regulate the expression level of p53, and the cooperation of p33ING1b gene is also needed in the process of p53 exerting normal function. Phosphorylation and acelylation are two important mechanisms to modulate p53 activity in vivo. Several dozen downstream genes are controlled directly by p53, and the activity of p53 falls into four categories: cell cycle inhibition, apoptosis, genetic stability, and inhibition of blood vessel formation. Elucidation of the function of p53 gene network will help to clarify the interaction mechanisms of p53 gene and its function-related genes.
Zhu
Zhi
Z
Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, PR China.
Zhu
Ming-Hua
MH
D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051736:Proto-Oncogene Proteins c-mdm2; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D025521:Tumor Suppressor Proteins
C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C115051:TP63 protein, human; C000606460:TP73 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2