Apoptosis Database

Description [+]

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

References [+]

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.

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 [+]

Evolution [+]

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:0005515	protein binding	mollecular_function	IPI
GO:0005741	mitochondrial outer membrane	cell_component	EXP
GO:0005739	mitochondrion	cell_component	IDA

KEGG Pathways [+]

Information from other databases [+]

Gene related links:

Protein related links:

Gene and disease information from OMIM: (For a full disease description table, click here.)

Other links

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PUMA (Homo sapiens)