How does P 53 turn on transcription?
p53 is a transcription factor, a protein that turns genes on. The animation illustrates how p53 recognizes and binds to a promoter, a specific region of DNA that initiates the transcription of the adjacent gene. After binding to the promoter, p53 recruits an RNA polymerase to transcribe the gene into mRNA.
What does MDM2 amplification mean?
MDM2 amplification by FISH is designed to detect amplification of the MDM2 gene to aid in patient diagnosis of soft tissue and bone tumors. In soft tissue tumors, MDM2 amplification is a frequent and specific finding in well differentiated liposarcoma/atypical lipomatous tumor (ref.
When DNA replication is blocked p53 becomes phosphorylated on?
Upon DNA damage, however, p53 becomes phosphorylated on serine-15 in vivo and no longer interacts with Mdm2 effectively (Siliciano et al., 1997; Shieh et al., 1997). The half-life of p53 is therefore prolonged due to the fact that it is no longer degraded in a Mdm2-dependent fashion.
Does p53 bind to DNA?
p53 tumor suppressor binds to DNA using all four of its arms. The typical binding site for the whole molecule is composed of three parts: a specific binding site for two p53 domains, a variable stretch of 0 to 13 base pairs, and a second specific binding site for the other two p53 domains.
What role does the p53 protein play in DNA repair?
p53 plays a prominent role as a facilitator of DNA repair by halting the cell cycle to allow time for the repair machineries to restore genome stability. In addition, p53 took on diverse roles to also directly impact the activity of various DNA-repair systems.
How does MDM2 regulate stability of p53?
MDM2 negatively regulates p53 by targeting the ubiquitin ligase activity of MDM2. A complementary approach to prevent p53 degradation by MDM2 is to develop agents designed to inhibit the E3 ligase activity of MDM2 directly so as to mimic the effects of ARF or the ribosomal protein L11.
Does p53 bind to MDM2?
MDM2 directly binds to the transactivation domain of p53 and inhibits its transcriptional activity, causes the ubiquitination and proteasomal degradation of p53, and exports p53 out of the nucleus which promotes p53 degradation and inhibits its activity.