Disease relevance of BH2 Radical

• The hybrid cell line BH2 was derived by fusion between an AKR thymoma BW5147 (HGPRT-) and C57BL thymoma EL-4R (TK-) [1].
• Membrane characteristics of parental thymic lymphoma cells (BW5147, EL-4R) and their hybrids (BH2) derived by PEG-promoted cell fusion were compared [2].

High impact information on BH2 Radical

• The EGL-1 protein contains a nine amino acid region similar to the Bcl-2 homology region 3 (BH3) domain but does not contain a BH1, BH2, or BH4 domain, suggesting that EGL-1 may be a member of a family of cell death activators that includes the mammalian proteins Bik, Bid, Harakiri, and Bad [3].
• Both yeast two-hybrid screening and lambda expression cloning identified a novel interacting protein, Bad, whose homology to Bcl-2 is limited to the BH1 and BH2 domains [4].
• Using site-specific mutagenesis, we show here that the amino-acid residues critical for protection of cells by Bcl-XL against Sindbis virus-induced apoptosis are clustered within the Bcl-2-homology regions 1 and 2 (BH1 and BH2 regions) [5].
• The three functionally important Bcl-2 homology regions (BH1, BH2 and BH3) are in close spatial proximity and form an elongated hydrophobic cleft that may represent the binding site for other Bcl-2 family members [6].
• A related protein that promotes cell death, Bax, wrestles with Bcl-2 through conserved motifs, BH1 and BH2, establishing a set point for these deaths [7].

Biological context of BH2 Radical

• BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax [8].
• A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions [9].
• The overall amino acid sequence identity between KSbcl-2 and other Bcl-2 homologs is low (15-20%) but concentrated within the BH1 and BH2 regions [10].
• The larger, more C-terminal region (within residues 90 to 203) encompassed, but extended beyond, two oligopeptide motifs called BH1 and BH2, which are known to mediate dimerization of Bc12 and related proteins [11].
• Molecular modeling showed that BFL-1 could have a similar core structure as BCL-xL, consisting of seven alpha helices, although both proteins share only the conserved BCL-2 homology domains (BH1 and BH2 domains), but otherwise have very limited sequence homology, particularly in the N-terminal region [12].

Anatomical context of BH2 Radical

• 7,8-Dihydrobiopterin (BH2) also increased BH4 levels and PC12 cell proliferation, both of which were reversed by methotrexate, which blocks the conversion of BH2 to BH4 by dihydrofolate reductase [13].
• The hybrid cells showed a near-tetraploid modal number of chromosomes, in contrast to the near-diploid stem-lines of both parental cell populations; most of the BH2 hybrid cells acquired marker chromosomes from both parental cell lines [1].
• 3. Pretreatment of RAW 264.7 macrophages with the BH4 precursor, dihydrobiopterin (BH2, 0.1 mM) did not restore nitrite formation in the presence of NAS (1 mM) [14].
• T-cell hybrids. II. BH2 line-derivation by fusion between two (BW5147 X EL-4R) thymoma lines [15].
• Isoelectric focusing of the cell populations, titration of membrane proton binding groups and quantitative examination of cell-substrate adhesiveness indicated that the BW5147 cells behaved as dominant in determining cell membrane characteristics of the BH2 hybrids [2].

Associations of BH2 Radical with other chemical compounds

• Bax proteins expressing alanine substitutions of the highly conserved amino acids glycine 108 in BH1, tryptophan 151 and 158 in BH2, and glycine 67 and aspartic acid 68 in BH3 retained their ability to promote chemotherapy-induced cell death that was inhibited by Bcl-XL and to form heterodimers with Bcl-XL [16].
• Since BH2 lacks cofactor activity, this was not required to modulate either the phosphorylation or the phenylalanine-activation of the hydroxylase [17].
• We have also determined the conformation and distances to the catalytic non-heme iron of both L-Trp and the tetrahydrobiopterin cofactor analogue L-erythro-7,8-dihydrobiopterin (BH2) bound to Delta90TPH by using 1H NMR spectroscopy [18].
• The rate of cyclic AMP-dependent phosphorylation of phenylalanine 4-mono-oxygenase was inhibited only by those pterins [(6R)-BH4, (6S)-BH4 and 7,8-dihydrobiopterin (BH2)] that were able to decrease the potency and efficiency of phenylalanine as an allosteric activator of the hydroxylase [17].
• Dihydrobiopterin (BH2) was found to inhibit the hydroxylation reaction and quenched the intrinsic tryptophan fluorescence of the enzyme with the same concentration dependence as that observed with (6S)-BH4 [19].

Gene context of BH2 Radical

• The BCL2L12 protein contains one BH2 homology domain, one proline-rich region similar to the TC21 protein and, five consensus PXXP tetrapeptide sequences [20].
• All BCL2 homology domains (BH1, BH2, BH3, and BH4) in bovine BCL2A1 were conserved as well as in other mammalian BCL2A1 [21].
• Neither the BH1 nor the BH2 domain of Bax was required for binding to the wild-type Bcl-2 and Bax proteins [22].
• We identified a short splicing variant of the MCL-1 mRNA in the human placenta encoding a protein, termed MCL-1 short (MCL-1S), with an altered C terminus as compared with the full-length MCL-1 long (MCL-1L), leading to the loss of BH1, BH2, and the transmembrane domains [23].
• N-Bak is generated by neuron-specific splicing of a novel 20-base pair exon, which changes the previously described Bak, containing Bcl-2 homology (BH) domains BH1, BH2, and BH3, into a shorter BH3-only protein [24].

Analytical, diagnostic and therapeutic context of BH2 Radical

• By GenBank database searches and PCR, we have identified a novel human Bcl2-like gene, Bcl2-L-10, which contains conserved BH4, BH1 and BH2 domains but lacks BH3 domain [25].
• Immunoprecipitation studies revealed that Bax with deletions in BH1 and BH2 still associated with wild-type Bax while deletion of BH3 disrupted Bax homodimerization [26].
• METHODS: An initial survey was conducted with reverse transcription-polymerase chain reaction (RT-PCR), using oligonucleotides against identified members of this family and against the conserved BH1 and BH2 domains [27].
• Molecular cloning, physical mapping, and expression analysis of a novel gene, BCL2L12, encoding a proline-rich protein with a highly conserved BH2 domain of the Bcl-2 family [20].
• 4. Based on 16S rRNA gene sequence analysis and other physiological characteristics, strain BH2 constitutes a new species within the genus Ferroplasma [28].

References