Disease relevance of BBC3

• BBC3 mediates fenretinide-induced cell death in neuroblastoma [1].
• Degradation of the proapoptotic proteins Bik, Puma, and Bim with Bcl-2 domain 3 homology in Chlamydia trachomatis-infected cells [2].
• This delicate balance can be tipped via induction of Puma in a p53-dependent matter, the level of which may vary between groups of patients with a different tendency for disease progression [3].
• Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation [3].
• In protoplasts isolated from nonacclimated rye leaves (Secale cereale L. cultivar Puma), cooling to -- 10 degrees C at a rate of 1 degrees C/min results in extensive freeze-induced dehydration (osmotic contraction), and injury is manifested as the loss of osmotic responsiveness during warming [4].

High impact information on BBC3

• Bim and Puma bind all the pro-survival proteins, whereas others, such as Noxa and Bad, engage distinct subsets and exhibit complementary killing [5].
• Within the Bcl-2 family, distinct apoptogenic BH3-only members like Bid, Bim, and Puma appear to function in specific cell death pathways [6].
• In contrast, Puma is considered the key mediator of p53-induced apoptosis [7].
• Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak [8].
• Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy [8].

Chemical compound and disease context of BBC3

• It has been reported that all major chlamydial species can inhibit host cell apoptosis and the Chlamydia trachomatis antiapoptotic activity is correlated with inhibition of activation of the proapoptotic multidomain Bcl-2 proteins Bax and Bak and degradation of BH3-only domain Bcl-2 proteins such as Puma [9].
• Inadvertent ingestion of thiafentanil oxalate by a captive adult female mountain lion (Puma concolor) caused a prolonged clinical syndrome that included sedation and depression, muscle tension, and myopathy that was incompletely antagonized by naltrexone HCl [10].

Biological context of BBC3

• Finally we demonstrated that BBC3 alone is sufficient to induce cell death in the 4-HPR-sensitive and resistant NB cell lines, and that siRNA against BBC3 significantly decreases apoptosis induced by 4-HPR [1].
• Their binding sites were mapped to BH3 (Bcl-2 homology) domain of Puma and BH1 domain of Mcl-1, respectively [11].
• In cells infected with a Chlamydia trachomatis L2 strain, Bim, Puma, and Bad were degraded with similar kinetics, and the degradation of all three was blocked by inhibition of the proteasome [12].
• In contrast, parental 697 cells underwent typical apoptosis with up-regulation of Puma and Noxa proteins, followed by cytochrome c release and caspase-3/7 activation after treatment with topoisomerase inhibitor in the presence or absence of BSO [13].
• Notably, we showed that proteasome-mediated down-regulation of Puma and Noxa proteins occurs in 697-Bcl-2 cells after treatment with BSO plus topoisomerase inhibitor, although there is an increase in the protein levels of p53 in these 697-Bcl-2 cells [13].

Anatomical context of BBC3

• Furthermore, the induction of BBC3 was associated with the sensitivity to this agent in the cell lines tested [1].
• Mcl-1 and Puma was shown to colocalize at the mitochondria by immunostaining [11].
• Here we reported that myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic member of the Bcl-2 family with a rapid turnover rate, interacts with Puma [11].
• In normal cells, Puma but not Noxa induces mitochondrial outer membrane permeabilization (MOMP), and this function is mediated in part by a pathway that involves calcium release from the endoplasmic reticulum (ER) and the subsequent caspase activation [14].
• Interestingly, although mTOR activation and Puma induction were observed in dying syncytia and neurons, IkB phosphorylation and TG2 up-regulation were only found in syncytia [15].

Associations of BBC3 with chemical compounds

• Among a panel of p53 target genes tested by quantitative PCR, the gene showing the largest defect in induction by 5FU was BBC3 (PUMA), which was induced 4-fold by wild type p53 and 2-fold by the N6A mutant [16].
• As shown recently, this inhibition is in part explained by the proteolytic degradation of the proapoptotic Bcl-2 family members (BH3-only proteins) Bim, Puma, and Bad upon chlamydial infection [12].
• In adriamycin-treated BALB/3T3 cells, the down-shift in temperature from 37 degrees C to 32 degrees C increased the Bcl-xL protein level and decreased the mRNA level of Puma and mitochondrial translocation of Bax, suppressing caspase-9-mediated apoptosis [17].
• Treatment of CLL cells with fludarabine induced only the proapoptotic genes Bax and Puma in a p53-dependent manner [3].
• Moreover, inhibition of the p53 abrogated the induction of Puma and promotion of apoptosis due to 6-hydroxydopamine treatments [18].

Other interactions of BBC3

• Two DNA damage-related pro-apoptotic proteins, Puma and Noxa, were upregulated in a dose- and time-dependent manner [19].
• TLE-1 and BBC3/PUMA were identified as direct targets of SOX4 [20].

Analytical, diagnostic and therapeutic context of BBC3

• The Puma/Mcl-1 interaction was verified by both yeast two-hybrid assay and co-immuno-precipation studies [11].
• Ribulose bisphosphate carboxylase--oxygenase (RUBPCase) from leaves of cold-hardened and unhardened Puma rye was purified by gel filtration and ion exchange chromatography [21].
• The quaternary structures of ribulose-1,5-bisphosphate carboxylase-oxygenase from cold-hardened and unhardened Puma rye were examined by two-dimensional gel electrophoresis according to the method of O'Farrell [22].
• Gastrointestinal helminths of free-ranging Florida panthers (Puma concolor coryi) and the efficacy of the current anthelmintic treatment protocol [23].

References