Disease relevance of TPD52L1

• D53 (TPD52L1) is a cell cycle-regulated protein maximally expressed at the G2-M transition in breast cancer cells [1].
• This may partially explain the protective effect of D53 immunostimulant against respiratory tract infection [2].
• D53 (Immucytal) is a compositive vaccine made of immunogenic ribosomes extracted from 4 bacterial species (Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes and Streptococcus pneumoniae) associated with a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (MPG-Kp) [3].

High impact information on TPD52L1

• Further examination of the three-dimensional structure in this region revealed conformational differences between human and murine beta2m that affect the ability of an aspartic acid residue at position 53 (D53) conserved in both beta 2ms to form an ionic bond with arginine residues at positions 35 and 48 of the heavy chain [4].
• Two human homologues of hD52, hD53 and hD54, have also been identified, demonstrating the existence of a novel gene/protein family [5].
• We now report that D53 expression is highly upregulated at the G2-M transition in breast cancer cell lines in which D53 is endogenously or exogenously expressed [1].
• These results identify D53 as a cell cycle-regulated protein whose deregulated expression can adversely affect the completion of mitosis [1].
• Interactions between D53 and 14-3-3, a negative regulator of the G2-M transition, were increased in synchronized populations enriched for cells in G2/M phases, compared with G1/S arrested cells [1].

Biological context of TPD52L1

• Alternative splicing as a mechanism for regulating 14-3-3 binding: interactions between hD53 (TPD52L1) and 14-3-3 proteins [6].
• Since the TPD52L1 gene is found at human chromosome 6q22-->q23, the mouse and human TPD52L1 loci are syntenically conserved [7].
• The human D52 locus has been previously mapped to chromosome 8q21, and using in situ mapping in the present study, a human D53 locus was mapped to chromosome 6q22-q23 [8].
• Dimerization was not observed using a D53A mutant of CovR, indicating that D53 is the site of phosphorylation in CovR [9].
• The essential amino acid residues identified in this work could be part of the PON1 active site, acting either as calcium ligands (E52 and D53?) or as substrate binding (W280?) or nucleophilic (His residues?) sites [10].

Anatomical context of TPD52L1

• Co-expressed hD53 and 14-3-3 proteins were similarly demonstrated to co-localise within the cytoplasm of breast carcinoma cell lines [6].
• Following subcellular fractionation, endogenous D53 was specifically detected in the membrane-containing fraction of PC12 cells, where it co-immunoprecipitated with Sb2 [11].
• Analysis by confocal microscopy showed that, in these cells, endogenous D53 co-localized partially with the transferrin receptor in early endosomes [11].
• A bacterial lysate (OM-85 BV), a preparation of purified bacterial ribosomes (D53) and a placebo were tested for ability to induce the local appearance of specific antibody-containing cells [12].
• Immunomodulation of polymorphonuclear leukocytes by D53 Immucytal and its constitutive fractions [3].

Associations of TPD52L1 with chemical compounds

• Twelve amino acids among conserved His and Asp/Glu residues were found essential for PON1 arylesterase and organophosphatase activities: H114, H133, H154, H242, H284, D53, D168, D182, D268, D278, E52, and E194 [13].
• We conclude that D53 immunostimulant in vivo primes AM to produce IL-1 following low LPS concentration stimulation [2].
• Chemotherapy consisting of cisplatin infusion (30 mg/m2) and Docetaxel (40 mg/m2) was given twice a week simultaneously with-irradiation during the whole treatment period (6-8 weeks) as follows: Cisplatin (D1,D8,D15,D22, D25,D36,D43,D50) and Docetaxel (D4, D11, D18, D25, D32, D39, D46, D53) [14].
• In this work we have studied the effect of the compound on human polymorphonuclear leukocyte (PMN) function "in vitro". We have demonstrated that D53 was able to significantly increase Fc- receptor dependent phagocytosis without modify the C3-receptor dependent activity [3].

Other interactions of TPD52L1

• As predicted from the distribution of 14-3-3 binding motifs in four hD52-like bait proteins tested, only a hD53 isoform encoding a 14-3-3 binding motif bound both 14-3-3beta and 14-3-3zeta preys in the yeast two-hybrid system [6].
• In situ mapping placed the hD54 gene on human chromosome 20q13.2-q13.3, a localization distinct from those of both hD52 and hD53 genes [15].
• The timing and subcellular localization of D53 expression paralleled that of cyclin B1, and D53 expression was similarly regulated at both post-transcriptional and post-translational levels [1].

Analytical, diagnostic and therapeutic context of TPD52L1

• Using soluble protein extracts from breast carcinoma cell lines, pull-down assays replicated interactions between recombinant 14-3-3beta and 14-3-3zeta isoforms and exogenously expressed hD53, and co-immunoprecipitation analyses demonstrated interactions between endogenous 14-3-3 and both endogenously and exogenously-expressed hD53 protein [6].
• Then, subjects were randomized to receive D53 (n = 6) or its placebo (n = 6) by both oral and subcutaneous injection routes from day 1 to day 15 [2].
• Slightly higher numbers were observed after treatment with OM-85 BV, but significant increases were noted only for the elevated numbers of specific antibody-containing cells observed after D53 therapy [12].
• Using site-directed mutagenesis and expression in human 293T cells, we have identified the following eight amino acids as being essential to PON1 activity: W280, H114, H133, H154, H242, H284, E52 and D53 [16].

References