Disease relevance of SIL1

• Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy [1].
• We found nine distinct mutations that would disrupt the SIL1 protein in individuals with Marinesco-Sjögren syndrome, an autosomal recessive cerebellar ataxia complicated by cataracts, developmental delay and myopathy [1].
• In contrast, CTNNB1 mutations were identified in 3 of 9 (33%) MSI-H and 10 of 20 (50%) MSS/MSI-L endometrial carcinomas, suggesting a more generalized involvement in these tumors [2].
• No differences were noted between groups in the MSS category, except for NSAIDs, which more patients in the nonspecific chest pain group used than in the fall-coded group (6.44% vs 5.63%; P<0.002) [3].
• A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer [4].

High impact information on SIL1

• We identified four disease-associated, predicted loss-of-function mutations in SIL1, which encodes a nucleotide exchange factor for the heat-shock protein 70 (HSP70) chaperone HSPA5 [5].
• The gene disrupted in Marinesco-Sjögren syndrome encodes SIL1, an HSPA5 cochaperone [5].
• It has been difficult to determine whether these BiP-associated molecules represent assembly intermediates which will be displaced from BiP and transported from the cell, or whether these are aberrant proteins that are ultimately degraded [6].
• MSI, defined as MSI high (MSI-H) or MSI-low/microsatellite stable (MSI-L/MSS), was assessed in tumors of 1,202 cases [7].
• All point mutations in MSI-H cancers were transitions, whereas 64% of those in MSS/MSI-L cancers were transversions (P < 0.01) [2].

Biological context of SIL1

• BAP encoded an approximately 54-kDa protein with an N-terminal endoplasmic reticulum (ER) targeting sequence, two sites of N-linked glycosylation, and a C-terminal ER retention sequence [8].
• Together, these data demonstrate that BAP serves as a nucleotide exchange factor for BiP and provide insights into the mechanisms that control protein folding in the mammalian ER [8].
• These residues, Tyr248, Tyr357, and Tyr462, were also found to be the major sites for Btk-dependent phosphorylation of BAP/TFII-I in vivo [9].
• Four weeks of living high-training low improves sea-level running performance in trained runners due to altitude acclimatization (increase in red cell mass volume and VO2 max) and maintenance of sea-level training velocities, most likely accounting for the increase in velocity at VO2 max and MSS [10].
• Maternal serum markers for trisomy 21 screening (MSS) can be assayed in women > or =35 years in an attempt to reduce the need for invasive procedures and thereby avoid their side effects [11].

Anatomical context of SIL1

• Identification of SIL1 mutations implicates Marinesco-Sjögren syndrome as a disease of endoplasmic reticulum dysfunction and suggests a role for this organelle in multisystem disorders [1].
• Two silica-precipitating peptides, silaffin-1A(1) and-1A(2), both encoded by the sil1 gene from the diatom Cylindrotheca fusiformis, were extracted from cell walls and purified to homogeneity [12].
• BAP/TFII-I, a protein implicated in transcriptional regulation, is associated with Btk in B cells and is transiently phosphorylated on tyrosine following B cell receptor engagement [9].
• Mutation of either Tyr248, Tyr357, or Tyr462 to phenylalanine reduced transcription from a c-fos promoter relative to wild-type BAP/TFII-I in transfected COS-7 cells, consistent with the interpretation that phosphorylation at these sites contributes to transcriptional activation [9].
• The percentage of patients in each group receiving medications (at the time of the outpatient encounter) that affect the cardiovascular system (CVS), central nervous system (CNS), or musculoskeletal system (MSS) was compared with Bonferrom-adjusted P values [3].

Associations of SIL1 with chemical compounds

• In particular, SBP-DPSCs differentiated into pre-osteoblasts, showing diffuse positivity for ALP, BAP, RUNX-2, and calcein [13].
• A 5,000-m time trial was the primary measure of performance; laboratory outcomes included maximal O2 uptake (VO2 max), anaerobic capacity (accumulated O2 deficit), maximal steady state (MSS; ventilatory threshold), running economy, velocity at VO2 max, and blood compartment volumes [10].
• However, when the protocalluses from line M 2 were treated with thidiazuron (TDZ) in a first culture step, and with BAP in a second step, the shoot formation frequency rose to 22% [14].
• The calli showed differentiation of globular structure embryos when transferred to MS medium containing 2,4-D 0.5mgl(-1) and BAP 1.0mgl(-1) [15].
• Plantlets were obtained in WPM medium and 10 gL-1 of sucrose with no plant regulator, or using 0.1 mgL-1 BAP and 0.5 mgL-1GA [16].

Co-localisations of SIL1

• Immunofluorescence staining demonstrated that BAP co-localized with GRP94 in the endoplasmic reticulum [8].

Other interactions of SIL1

• Interestingly, recent genetic work has linked mutations in the human and murine SIL1 genes to neurodegeneration, and mutations in the human SEC63 gene to autosomal dominant polycystic liver disease [17].

Analytical, diagnostic and therapeutic context of SIL1

• Using this multiplex polymerase chain reaction (PCR) system 29 colorectal tumour tissues with known MSI status could be unambiguously identified as MSI-H (13 cases) or MSI-L/MSS (16 cases) [18].
• A direct fluorescent antibody (DFA) method was compared with methenamine silver staining (MSS) for the detection of Pneumocystis carinii in 384 cytological specimens [19].
• HPV16 detection was better with PCR than Southern blot, particularly for SIL 1 and SIL 2 [20].

References