Disease relevance of DEDD

• With deft management of such challenges by local, national, and international health authorities, poliomyelitis, a disease that threatened children everywhere just 2 generations ago, could soon be relegated to history like smallpox before it [1].
• The clinical examination included registration of decayed, extracted and filled teeth and surfaces (deft and defs), gingival bleeding points (GBI) and presence of open bite or crossbite [2].
• We hypothesized that some highly exposed persistently seronegative (HEPS) individuals might have intact theta;-defensin (DEFT) genes and produce functional theta;-defensins that might account for their resistance to HIV-1 infection [3].
• The etiology of clefting per se--isolated deft palate versus cleft lip with or without deft palate--did not seem to explain the associations between dental arch dimensions and the studied misarticulations [4].
• Shoulder dystocia is an infrequent and unexpected emergency requiring rapid and deft solution [5].

High impact information on DEDD

• Searching for molecules potentially able to block DR death-inducing signaling complex (DISC), we found that primitive neural cells expressed high levels of the death effector domain-containing protein PED (also known as PEA-15) [6].
• Many viruses express antiapoptotic proteins, including caspase inhibitors, Bcl-2 homologues and death-effector-domain-containing proteins that are termed FLIPs (FLICE [Fas-associated death-domain-like IL-1beta-converting enzyme]-inhibitory proteins) [7].
• Early in apoptosis, both cytosolic DEDD and its close homologue DEDD2 formed filaments that colocalized with and depended on K8/18 and active caspase-3 [8].
• In addition, both caspase-3 activation and K18 cleavage was inhibited by expression of DEDDDeltaNLS1-3, a cytosolic form of DEDD that cannot be ubiquitinated [8].
• DEDD regulates degradation of intermediate filaments during apoptosis [8].

Biological context of DEDD

• Consistent with its nuclear localization, DEDD contains two nuclear localization signals and the C-terminal part shares sequence homology with histones [9].
• MRIT, a novel death-effector domain-containing protein, interacts with caspases and BclXL and initiates cell death [10].
• Recent reports suggest that the highly conserved and ubiquitous death effector domain containing DNA binding protein (DEDD) plays a role in the recruitment of procaspase-9 and -3 at this CK8/18 scaffold [11].
• PEA-15 is a widely expressed death effector domain-containing phosphoprotein involved in signal transduction, apoptosis, ERK activation, and glucose transport [12].
• The peptides included rhesus theta defensins (RTDs) 1 to 3, originally isolated from rhesus macaque leukocytes, and three peptides (retrocyclins 1 to 3) whose sequences were inferred from human theta-defensin (DEFT) pseudogenes [13].

Anatomical context of DEDD

• In situ hybridization analysis further indicated the expression of DEFT mRNA in meiotic male germ cells [14].
• Northern blot hybridization experiments have shown that the DEFT messenger RNA (mRNA) is expressed in a variety of human and rat tissues, with particularly abundant expression in the testis [14].
• DEDAF interacts with FADD, procaspase-8, and procaspase-10 in the cytosol as well as with the DED-containing DNA-binding protein (DEDD) in the nucleus [15].
• In cell lines MCF-7 and Jurkat, the overexpression of DEDDL could induce apoptosis more potently than that of DEDD [16].
• For example, among 6-yr-olds a mean number of 11.8 defs and 5.2 deft was observed and 82% of the children were affected by caries in primary teeth [17].

Associations of DEDD with chemical compounds

• We now demonstrate that many of its 16 lysine residues can serve as alternative acceptors for ubiquitination to maintain the monoubiquitination status of DEDD [18].
• In cells showing a filamentous staining pattern, DEDD was strongly associated with the CK8/18 cytokeratin filaments as evidenced by double immunofluorescence and its resistance to extraction with Triton X-100 [11].
• Caspase-10/a (Mch4) and caspase-10/b (FLICE2) are related death effector domain-containing cysteine aspartases presumed to be at or near the apex of apoptotic signaling pathways [19].
• In a regression analysis for the deft, the use of fluoridated salt (standardized coefficient SC=-0.25) and fluoride gel (SC=-0.37) showed the greatest effect, as did the fluoride gel (SC=-0.26) and gingival bleeding (SC=0.50) for the number of active carious lesions [20].
• During the last decade, several microbiological rapid methods or principles (DEFT, microcolonies, Limulus lysate, ATP, conductance, microcalorimetry, reduction of trimethylamine oxide (TMAO)) have been suggested for estimating the bacteriological quality of seafoods [21].

Physical interactions of DEDD

• DEDD interacts with both the CK8/18 intermediate filament network and procaspase-3 and -9 [11].

Other interactions of DEDD

• The DED in DEDD therefore represents a novel domain that is structurally similar to other DEDs but functionally different from classical DEDs found in FADD or caspase-8 [22].
• In the nucleus, DEDAF caused the DEDD protein to relocalize from subnuclear structures to a diffuse distribution in the nucleoplasm [15].
• When overexpressed, DEDD localizes to nucleoli-like structures, activates caspase-6 and specifically inhibits RNA polymerase I (Pol I) dependent transcription in vivo as shown by blockage of BrUTP incorporation [22].
• CLARP, a death effector domain-containing protein interacts with caspase-8 and regulates apoptosis [23].
• DEDD association with cytokeratin filaments correlates with sensitivity to apoptosis [11].

Analytical, diagnostic and therapeutic context of DEDD

• Using a new anti-DEDD antibody that allows us to stain endogenous DEDD in immunofluorescence microscopy we now detect a significant amount of DEDD in nucleoli of all cells tested [22].
• Studies with the synthetic autoinhibitory domain peptides of CaM-kinase II indicate that CaM-kinase IV has a similarly located autoinhibitory domain, and this was confirmed since site-directed mutagenesis of this region (HMDT308 to DEDD and FN317 to DD) generated fully active Ca2+/CaM-independent kinases [24].
• That DEDDL could bind FADD and cFLIP more potently than DEDD in vivo was revealed by cotransfection and immunoprecipitation [16].
• An unhurried, deft, economical technique allied to efficient use of available resources, surgical instruments and support staff is the hallmark of a 'good' surgeon [25].

References