negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator
Definition
Target type: biologicalprocess
Any process that stops, prevents or reduces the frequency, rate or extent of intrinsic apoptotic signaling pathway by p53 class mediator. [GOC:BHF, GOC:mtg_apoptosis, GOC:rl, GOC:TermGenie, PMID:15705871]
The p53 protein is a well-known tumor suppressor that plays a crucial role in regulating cellular responses to stress. When cells encounter DNA damage, hypoxia, or other stressors, p53 is activated and can trigger various cellular responses, including cell cycle arrest, DNA repair, and apoptosis.
Apoptosis, or programmed cell death, is a tightly regulated process that eliminates damaged or unwanted cells from the body. This process is essential for maintaining tissue homeostasis and preventing the development of cancer. Apoptosis can be initiated by two main pathways: the extrinsic pathway, which is triggered by external signals like death ligands, and the intrinsic pathway, which is triggered by intracellular signals like DNA damage.
The intrinsic apoptotic pathway, also known as the mitochondrial pathway, is initiated by the release of cytochrome c from the mitochondria into the cytosol. Cytochrome c then binds to the adaptor protein Apaf-1, which activates caspase-9, an initiator caspase. Caspase-9 then activates downstream executioner caspases, such as caspase-3 and caspase-7, which dismantle the cell's structure and lead to cell death.
p53 can negatively regulate the intrinsic apoptotic signaling pathway in several ways.
One way is by activating the expression of pro-survival genes, such as Bcl-2 and Bcl-xL, which are anti-apoptotic proteins. Bcl-2 and Bcl-xL inhibit the release of cytochrome c from the mitochondria, preventing the activation of the caspase cascade and apoptosis.
Another way p53 can negatively regulate the intrinsic apoptotic pathway is by inhibiting the expression of pro-apoptotic genes, such as Bax and Bak. Bax and Bak are pro-apoptotic proteins that promote the release of cytochrome c from the mitochondria. By inhibiting the expression of these genes, p53 can prevent the activation of the intrinsic apoptotic pathway.
In addition, p53 can also directly interact with and inhibit the activity of pro-apoptotic proteins, such as Apaf-1 and caspase-9.
Overall, p53 plays a critical role in maintaining cellular homeostasis and preventing the development of cancer. By negatively regulating the intrinsic apoptotic signaling pathway, p53 can prevent premature cell death and promote cellular survival. However, when p53 is mutated or inactive, this can lead to uncontrolled cell growth and cancer development.'
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Ribonucleoside-diphosphate reductase subunit M2 B | A ribonucleoside-diphosphate reductase subunit M2 B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q7LG56] | Homo sapiens (human) |
| E3 ubiquitin-protein ligase Mdm2 | An E3 ubiquitin-protein ligase Mdm2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q00987] | Homo sapiens (human) |
Compounds (22)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| catechol | catechols | allelochemical; genotoxin; plant metabolite | |
| gossypol | Gossypol: A dimeric sesquiterpene found in cottonseed (GOSSYPIUM). The (-) isomer is active as a male contraceptive (CONTRACEPTIVE AGENTS, MALE) whereas toxic symptoms are associated with the (+) isomer. | ||
| quinone | 1,4-benzoquinone : The simplest member of the class of 1,4-benzoquinones, obtained by the formal oxidation of hydroquinone to the corresponding diketone. It is a metabolite of benzene. benzoquinone : The simplest members of the class of benzoquinones, consisting of cyclohexadiene which is substituted by two oxo groups. quinone : Compounds having a fully conjugated cyclic dione structure, such as that of benzoquinones, derived from aromatic compounds by conversion of an even number of -CH= groups into -C(=O)- groups with any necessary rearrangement of double bonds (polycyclic and heterocyclic analogues are included). | 1,4-benzoquinones | cofactor; human xenobiotic metabolite; mouse metabolite |
| vorinostat | vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL). Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME. | dicarboxylic acid diamide; hydroxamic acid | antineoplastic agent; apoptosis inducer; EC 3.5.1.98 (histone deacetylase) inhibitor |
| apomorphine | Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. | aporphine alkaloid | alpha-adrenergic drug; antidyskinesia agent; antiparkinson drug; dopamine agonist; emetic; serotonergic drug |
| uridine diphosphate | Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. | pyrimidine ribonucleoside 5'-diphosphate; uridine 5'-phosphate | Escherichia coli metabolite; mouse metabolite |
| cytidine diphosphate | Cytidine Diphosphate: Cytidine 5'-(trihydrogen diphosphate). A cytosine nucleotide containing two phosphate groups esterified to the sugar moiety. Synonyms: CRPP; cytidine pyrophosphate. | cytidine 5'-phosphate; pyrimidine ribonucleoside 5'-diphosphate | Escherichia coli metabolite; mouse metabolite |
| cytarabine | beta-D-arabinoside; monosaccharide derivative; pyrimidine nucleoside | antimetabolite; antineoplastic agent; antiviral agent; immunosuppressive agent | |
| nutlin 3 | stilbenoid | ||
| nutlin 2 | |||
| 1-aminoadenosine | 1-aminoadenosine: structure | ||
| nutlin 1 | nutlin 1: an MDM2 antagonist; structure in first source | ||
| nutlin-3a | nutlin 3: an MDM2 antagonist; structure in first source | stilbenoid | |
| MI-63 | MI-63 : An azaspiro compound resulting from the formal fusion of position 3 of 6-chloro-oxindole with position 3 of (2R,3SS5S)-3-(3-chloro-2-fluorophenyl)-5-(2,2-dimethylpropyl)-N-[2-(morpholin-4-yl)ethyl]pyrrolidine-2-carboxamide. It is a potent inhibitor of the MDM2-p53 interaction. | azaspiro compound; monochlorobenzenes; monofluorobenzenes; morpholines; oxindoles; pyrrolidines; secondary carboxamide | apoptosis inducer |
| nutlin-3b | Nutlin; piperazinone | anticoronaviral agent | |
| pb 12 | |||
| spautin-1 | |||
| nvp-cgm097 | NVP-CGM097: an MDM2 and HDM2 inhibitor; structure in first source | ||
| rg7388 | RG7388: structure in first source | ||
| sar405838 | SAR405838: an inhibitor of the interaction of MDM2 and p53; has antineoplastic activity; structure in first source | ||
| rg7112 | |||
| amg 232 |