Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.2.1.7 (BAL)
 1,977 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical risk factor models such as the International Prognostic Index are used to identify diffuse large B-cell lymphoma (DLB-CL) patients with different risks of death from their diseases. To elucidate the molecular bases for these observed clinical differences in outcome, differential display was used to identify a novel gene, termed BAL (B-aggressive lymphoma), which is expressed at significantly higher levels in fatal high-risk DLB-CLs than in cured low-risk tumors. The major BAL complementary DNA encodes a previously uncharacterized 88-kd nuclear protein with a duplicated N-terminal domain homologous to the nonhistone portion of histone-macroH2A and a C-terminal alpha-helical region with 2 short coiled-coil domains. Of note, the BAL N-terminus and secondary structure resemble those of a recently identified human protein, KIAA1268. In addition, both BAL and KIAA1268 map to chromosome 3q21, further suggesting that these genes belong to a newly identified family. BAL is expressed at increased levels in DLB-CL cell lines with an activated peripheral B cell, rather than a germinal center B cell, phenotype. This observation and the characteristic dissemination of high risk DLB-CLs prompted studies regarding the role of BAL in B-cell migration. In classical transwell assays, stable BAL-overexpressing B-cell lymphoma transfectants had significantly higher rates of migration than vector-only transfectants, indicating that the risk-related BAL gene promotes malignant B-cell migration. (Blood. 2000;96:4328-4334)
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PMID:BAL is a novel risk-related gene in diffuse large B-cell lymphomas that enhances cellular migration. 1111 Jul 9

BAL1 (B-aggressive lymphoma 1) was originally identified as a risk-related gene in diffuse large B-cell lymphoma. BAL1 encodes a nuclear protein with N-terminal macro domains and a putative C-terminal poly(ADP-ribose) polymerase (PARP) active site. Macro domains are sequences homologous to the non-histone region of histone macroH2A. Several lines of evidence suggest that these domains may modulate transcription, including a high concentration of histone macroH2A in the inactive X chromosome, direct interference with transcription factor binding in a positioned nucleosome, and structural similarity to DNA binding domains. Poly(ADP-ribosyl)ation is a critical post-translational modification that regulates chromatin configuration and transcription. In this report we describe two additional BAL family members, BAL2 and BAL3, with N-terminal macro domains and putative C-terminal PARP active sites and assess the function of these specific regions in BAL family members. Herein, we demonstrate that BAL macro domains repress transcription when tethered to a promoter. In addition, we show that BAL2 and BAL3, but not BAL1, exhibit PARP activity. In agreement with these data, BAL1 lacks several critical donor and acceptor residues that are conserved in the BAL2 and -3 PARP active sites. Of interest, BAL family members with inactive or functional PARP domains differed in their ability to repress transcription. BAL family members are the only described proteins with both PARP and macro domains, underscoring the potential functional significance of this unique combination.
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PMID:B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity. 1606 77

Solid-phase synthesis is of tremendous importance for small-molecule and biopolymer synthesis. Linkers (handles) that release amide-containing products after completion of solid-phase synthesis are widely used. Here we present a new class of highly acid-labile backbone amide linkers (BAL handles) based on 3,4-ethylenedioxythiophene (EDOT), which we have termed T-BAL. These thiophene linkers are synthesized in three convenient steps from commercially available EDOT. In the linker design, the spacer was introduced to the EDOT core either via a carbon-carbon bond or via a thioether linkage. Introduction of the spacer via a C-C bond was performed by a chemoselective Negishi coupling without transient protection of the aldehyde group to provide the T-BAL1 handle. Introduction via a thioether linkage was performed by a facile nucleophilic aromatic substitution between the brominated EDOT aldehyde and unprotected mercapto acids to provide T-BAL2 and T-BAL3 handles. The minimal use of protecting groups gave the corresponding linker molecules in few synthetic steps and in good yields. After anchoring of the linker to a polymeric support, introduction of the first amino acid was achieved by reductive amination, giving a secondary amine. A following acylation of the secondary amine with a symmetrical amino acid anhydride resulted in a backbone amide linkage between the handle and the growing substrate (e.g., peptide chain). After solid-phase synthesis, the substrates could be released from the resin by either low acid conditions using 1% TFA in CH2Cl2 or high acid conditions such as 50% TFA in CH2Cl2. Peptide thioesters could be released from the T-BAL1 handle under very mild conditions using aqueous acetic acid. Tert-butyl based protecting groups, tert-butyl esters, tert-butyl ethers, and Boc groups, as well as dimethyl acetals were relatively stable to these mild conditions for release of the peptides.
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PMID:Thiophene backbone amide linkers, a new class of easily prepared and highly acid-labile linkers for solid-phase synthesis. 1693 22

Poly(ADP-ribos)ylation is one of the longest-known but most enigmatic posttranslational modifications transducing specific signals. The enzyme responsible for the majority of poly(ADP-ribose) polymerization in cells, PARP-1, promotes DNA repair but also mediates a caspase-independent form of apoptosis in response to stressors such as irradiation. However, the biologic function of most other PARPs is not known. Macro-PARPs constitute one branch of the large family of PARP-like proteins also designated as B aggressive lymphoma proteins (BAL1, 2a/2b, 3, or PARP-9, PARP-14, and PARP-15). To elucidate biologic role(s) of a BAL-family macro-PARP, we analyzed mice deficient in PARP-14, a binding partner of the IL-4-induced transcription factor Stat6. We show here that PARP-14 plays a fundamental role mediating protection against apoptosis in IL-4-treated B cells, including that after DNA damage, and mediates IL-4 effects on the levels of gene products that regulate cell survival, proliferation, and lymphomagenesis. Collectively, the results establish that PARP-14 mediates regulation of gene expression and lymphocyte physiology by IL-4 and has a function distinct from PARP-1. Furthermore, the findings suggest mechanisms by which BAL-family proteins might influence pathologic processes involving B lymphocytes.
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PMID:PARP-14, a member of the B aggressive lymphoma family, transduces survival signals in primary B cells. 1914 89