PUMA (Homo sapiens)
- Synonyms: PUMA, JFY1, PUMA, BBC3
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Bcl-2-binding component 3 (p53 up-regulated modulator of apoptosis)(JFY-1)
- Family: Bcl-2 family : BH3-only
- Process: apoptosis,
- Pathways: intrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Bbc3
- WIKI: PUMA-H_sapiens
- PUMA induces the rapid apoptosis of colorectal cancer cells.
- Yu J, Zhang L, Hwang PM, Kinzler KW, Vogelstein B
- Through global profiling of genes that were expressed soon after p53 expression, we identified a novel gene termed PUMA (p53 upregulated modulator of apoptosis). The protein encoded by PUMA was found to be exclusively mitochondrial and to bind to Bcl-2 and Bcl-X(L) through a BH3 domain. Exogenous expression of PUMA resulted in an extremely rapid and profound apoptosis that occurred much earlier than that resulting from exogenous expression of p53. Based on its unique expression patterns, p53 dependence, and biochemical properties, PUMA may be a direct mediator of p53-associated apoptosis. Mol Cell. 2001 Mar;7(3):673-82.
- PUMA, a novel proapoptotic gene, is induced by p53.
- Nakano K, Vousden KH
- The p53 tumor-suppressor protein functions as a transcriptional activator, and several p53-inducible genes that play a role in the induction of apoptosis in response to p53 have been described. We have identified a novel gene named PUMA (p53 upregulated modulator of apoptosis) as a target for activation by p53. This gene encodes two BH3 domain-containing proteins (PUMA-alpha and PUMA-beta) that are induced in cells following p53 activation. PUMA-alpha and PUMA-beta show similar activities; they bind to Bcl-2, localize to the mitochondria to induce cytochrome c release, and activate the rapid induction of programmed cell death. Antisense inhibition of PUMA expression reduced the apoptotic response to p53, and PUMA is likely to play a role in mediating p53-induced cell death through the cytochrome c/Apaf-1-dependent pathway. Mol Cell. 2001 Mar;7(3):683-94.
- Expression of bbc3, a pro-apoptotic BH3-only gene, is regulated by diverse cell death and survival signals.
- Han J, Flemington C, Houghton AB, Gu Z, Zambetti GP, Lutz RJ, Zhu L, Chittenden T
- BH3-only proteins function at a proximal point in a conserved cell death pathway by binding, through their BH3 domains, to other Bcl-2 family members and triggering mitochondrial events associated with apoptosis. Here, we describe a strongly pro-apoptotic BH3-only protein, designated Bbc3, whose expression increases in response to diverse apoptotic stimuli. bbc3 mRNA levels were induced by exposure to DNA-damaging agents and by wild-type p53, which mediates DNA damage-induced apoptosis. p53 transactivated bbc3 through consensus p53 binding sites within the bbc3 promoter region, indicating that bbc3 is a direct target of p53. Additionally, bbc3 mRNA was induced by p53-independent apoptotic stimuli, including dexamethasone treatment of thymocytes, and serum deprivation of tumor cells. Insulin-like growth factor-1 and epidermal growth factor, growth factors with broad anti-apoptotic activity, were each sufficient to suppress Bbc3 expression in serum-starved tumor cells. These results suggest that the transcriptional regulation of bbc3 contributes to the transduction of diverse cell death and survival signals. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11318-23.
- References from Mouse ortholog(s):
- p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa.
- Villunger A, Michalak EM, Coultas L, Mullauer F, Bock G, Ausserlechner MJ, Adams JM, Strasser A
- Apoptosis provoked by DNA damage requires the p53 tumor suppressor, but which of the many p53-regulated genes are required has remained unknown. Two genes induced by this transcription factor, noxa and puma (bbc3), stand out, because they encode BH3-only proteins, proapoptotic members of the Bcl-2 family required to initiate apoptosis. In mice with either noxa or puma disrupted, we observed decreased DNA damage-induced apoptosis in fibroblasts, although only loss of Puma protected lymphocytes from cell death. Puma deficiency also protected cells against diverse p53-independent cytotoxic insults, including cytokine deprivation and exposure to glucocorticoids, the kinase inhibitor staurosporine, or phorbol ester. Hence, Puma and Noxa are critical mediators of the apoptotic responses induced by p53 and other agents. Science. 2003 Nov 7;302(5647):1036-8. Epub 2003 Sep 18.
Structure & Sequence [+]
Protein sequence [+]
PUMA | Homo sapiens | 9606 | length:193
View protein alignment and tree with Jalview:
Explore tree at phylomeDB:   Click here.
Homologs list [+]
DeathBase uses Jalview, an external application that requires Java. Please, check that you have the latest version of Java installed and that Java is enabled in your browser. When correctly installed your browser should display the following examples properly. You can download the latest version of Java at Java Download Site.
Gene Ontology [+]
|GO id||Name||Ontology type||Evidence|
|GO:0042771||DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis||biological_proccess||IEA|
|GO:0006917||induction of apoptosis||biological_proccess||IDA|
|GO:0045926||negative regulation of growth||biological_proccess||IMP|
|GO:0001836||release of cytochrome c from mitochondria||biological_proccess||IDA|
|GO:0006919||activation of caspase activity||biological_proccess||IDA|
|GO:0005741||mitochondrial outer membrane||cell_component||EXP|
Check GO Evidence Codes here
KEGG Pathways [+]
Information from other databases [+]
- OMIM gene information: 605854
- OMIM disease information:
Click on [?] for more information.