Disease relevance of LRDD

• According to the results of the dark field microscopy, the % of spirochetes and motile rods in the periodontally diseased pockets was significantly higher in the PIDD than in the CIDD subjects (9.2 +/- 13.4% and 10.8 +/- 14.3% versus 4.0 +/- 5.2% and 3.1 +/- 3.2%, p < 0.01 and p < 0.001, chi 2-test, respectively) [1].
• Based upon their long-term medical records, 19 were identified as having poorly controlled (PIDD) and 10 as controlled insulin-dependent diabetes mellitus (CIDD) [2].

High impact information on LRDD

• Upon genotoxic stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappaB-activating kinase complex, NEMO, is formed [3].
• Previously, we reported a role for the p53-inducible death-domain-containing protein, PIDD, in caspase-2 activation and apoptosis in response to DNA damage [3].
• This assumption was further supported by siRNA transfections targeting PIDD or RAIDD [4].
• Upon intracellular processing, the C-terminal death domain-containing fragment of the p53-inducible PIDD/LRDD protein translocates to the nucleoli and interacts with nucleolin [5].
• PIDD patients had elevated plasma cell levels relative to controls and they appeared also to have a decreased collagen fiber density [2].

Biological context of LRDD

• PIDD mediates NF-kappaB activation in response to DNA damage [3].
• Increased PIDD expression resulted in spontaneous activation of caspase-2 and sensitization to apoptosis by genotoxic stimuli [6].
• Protein Inter-atomic Distance Distributions (PIDD) is a dedicated database and structural bio-informatics system for distance based protein modeling [7].

Anatomical context of LRDD

• In addition, fibroblasts occupied less volume in the ICT of PIDD patients than in controls [2].
• PIDD patients had the largest mean area of cross-section of the blood vessels, but this difference was not statistically significant (P > or = 0.211; t-test) [2].
• For each PIDD patient, respective volumetric and numeric densities of cellular components including fibroblasts, neutrophilic granulocytes, monocyte/macrophages, mast cells, lymphocytes, blast cells, and plasma cells were recorded in the inflamed connective tissue (ICT) [2].
• Swollen and proliferated endothelial cells were frequently found in PIDD patients and the mean distance from the lumen to the outer border of basement membrane was greater in the PIDD than in the controls (P < 0.001; t-test) [2].

Associations of LRDD with chemical compounds

• LRDD, a novel leucine rich repeat and death domain containing protein [8].
• The PIDD subjects exhibited higher mean blood glucose levels (12.9 +/- 4.6 mmol/l, mean +/- S.D.) than the CIDD subjects (7.9 +/- 3.6 mmol/l) (p < 0.001, t-test) [1].

Physical interactions of LRDD

• RAIDD has an N-terminal caspase recruitment domain (CARD) that interacts with the CARD of caspase-2 and a C-terminal death domain (DD) that interacts with the DD in PIDD [9].

Other interactions of LRDD

• Interestingly, LRDD is shown to interact with two other death domain containing proteins, FADD and MADD, presumably through death domain interactions [8].
• We show that activation of caspase-2 occurs in a complex that contains the death domain-containing protein PIDD, whose expression is induced by p53, and the adaptor protein RAIDD [6].
• This translocation is mediated by or leads to the interaction of the PIDD death domain with nucleolin, a protein important for rRNA processing within nucleoli and possibly involved in the DNA damage response [5].

References