Disease relevance of BCAP31

• We report two sisters with congenital myotonic dystrophy (CDM) born to a normal mother and an affected father [1].
• Decrement of the thymopsyche increased after both doses in the moderate hypoxic condition, while under marked hypoxia 6 mg CDM attenuated and 9 mg aggravated this deterioration [2].
• Mentzel T, Goodland JR, Smith MA, Fletcher CDM: Ancient hematoma: a unifying concept for a post-traumatic lesion mimicking an aggressive soft tissue neoplasm. Mod Pathol 1997;10:334-340 [3].
• Plates were overlaid with molten CDM (5 ml), containing 40 microg ml(-1) X-gal and approx. 1000 CFU ml(-1) of an overnight culture of E. coli SPC105 containing a chromosomal marOII::lacZ fusion [4].
• The diagnosis of CDM was suspected by ultrasound markers of borderline ventriculomegaly, polyhydramnios, and reduced fetal movements [5].

Psychiatry related information on BCAP31

• 6 mg and slightly less so 9 mg CDM attenuated this deterioration of vigilance (i.e. dynamic state of the neuronal network determining adaptive behavior) [2].

High impact information on BCAP31

• DOCK4 therefore encodes a CDM family member that regulates intercellular junctions and is disrupted during tumorigenesis [6].
• Here we show that DOCK2, a haematopoietic cell-specific CDM family protein, is indispensable for lymphocyte chemotaxis [7].
• PACS-2 controls the apposition of mitochondria with the ER, as depletion of PACS-2 causes BAP31-dependent mitochondria fragmentation and uncoupling from the ER [8].
• Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol [9].
• Here, we report that the p20 caspase cleavage fragment of BAP31 can direct pro-apoptotic signals between the ER and mitochondria [9].

Biological context of BCAP31

• Mutations in DXS1357E and the ABCD1 promoter region have not been described previously [10].
• Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: a novel neonatal phenotype similar to peroxisomal biogenesis disorders [10].
• The BAP31 gene is ubiquitously expressed in murine tissues and is located on the X chromosome in both mouse and man [11].
• Preferential recruitment of procaspase-8L by the BAP31 complex at the endoplasmic reticulum suggests an additional pathway for regulating initiator caspase-8 during apoptosis [12].
• Cleavage of BAP31 during apoptosis generates a p20 fragment that remains integrated in the membrane and, when expressed ectopically, is a potent inducer of cell death [13].

Anatomical context of BCAP31

• Export of cellubrevin from the endoplasmic reticulum is controlled by BAP31 [14].
• We conclude that BAP31 represents a novel class of sorting proteins that controls anterograde transport of certain membrane proteins from the ER to the Golgi complex [14].
• When microtubules were depolymerized with nocodazole, this accumulation disappeared and BAP31 was confined to the ER [14].
• Furthermore, a fraction of BAP31 and cellubrevin was complexed when each of them was quantitatively immunoprecipitated from detergent extracts of fibroblasts (BHK 21 cells) [14].
• During purification of clathrin-coated vesicles or early endosomes, BAP31 did not cofractionate with cellubrevin [14].

Associations of BCAP31 with chemical compounds

• As a result, cleavage of the caspase targets poly(ADP-ribosyl) polymerase and endogenous BAP31, as well as the redistribution of phosphatidylserine and fragmentation of DNA, was observed [13].
• Ca(2+) homeostasis and ER morphology were unaffected by the lack of calnexin, but ER stress-induced Bap31 cleavage was significantly inhibited [15].
• Bap31 is a polytopic integral membrane protein of the endoplasmic reticulum and forms a complex with Bcl-2/Bcl-XL and procaspase-8 (Ng, F. W. H., Nguyen, M., Kwan, T., Branton, P. E., Nicholson, W. D., Cromlish, J. A., and Shore, G. C. (1997) J. Cell Biol. 139, 327-338) [16].
• The chemistry of dinuclear analogues of the anticancer drug cisplatin. A DFT/CDM study [17].
• Factors governing the protonation state of Zn-bound histidine in proteins: a DFT/CDM study [18].

Physical interactions of BCAP31

• Here we report that CD11b/CD18 specifically binds to BAP31, a member of a novel class of sorting proteins regulating cellular anterograde transport [19].
• Immunoprecipitation experiments revealed that Bap31 forms complexes with calnexin, which may play a role in apoptosis [15].

Regulatory relationships of BCAP31

• The results suggest that calnexin may not play a role in the initiation of the ER stress but that the protein has an effect on later apoptotic events via its influence on Bap31 function [15].

Other interactions of BCAP31

• Based on comparisons between genomic and cDNA sequence, both the Xq28 creatine transporter and DXS1357E genes are transcriptionally active [20].
• Co-association of CD11b/CD18 and BAP31 was confirmed in co-immunoprecipitation and protein binding assays [19].
• Overexpression of the Bap31 homolog, Bap29, decreases surface class levels in HeLa, indicating that it does not substitute for Bap31 [21].
• We show that BAP31 specifically associates with nonmuscle myosin heavy chain B and nonmuscle gamma-actin, two components of the cytoskeleton actomyosin complex [22].
• BAP31 is a 28-kDa integral membrane protein of the endoplasmic reticulum whose cytosolic domain contains two identical caspase recognition sites (AAVD.G) that are preferentially cleaved by initiator caspases, including caspase 8 [13].

Analytical, diagnostic and therapeutic context of BCAP31

• When BHK cells were analyzed by immunocytochemistry, BAP31 did not overlap with cellubrevin, but rather colocalized with resident proteins of the ER [14].
• We describe here the characterization by capillary liquid chromatography microelectrospray tandem MS of a BAP31 immunocomplex isolated from a HepG2 cell lysate in the absence of a death signal [22].
• In a double-blind, placebo-controlled trial, human brain function and mental performance were studied under two different degrees of hypoxia after administration of two different doses (6 mg and 9 mg) of co-dergocrine mesylate (CDM) utilizing blood gas analysis, EEG mapping and psychometry [2].
• Rapid cytochrome c release, activation of caspases 3, 6, 7 and 8 followed by Bap31 cleavage in HeLa cells treated with photodynamic therapy [23].
• This case highlights the importance of ultrasound markers for the diagnosis of CDM in the absence of definitive prenatal diagnosis [5].

References