High impact information on MCRS1

• This PTEN-mediated inhibition of cellular transformation requires physical interaction as evidenced by the failure of PTEN(T366A) point mutation (residing within the MSP58 interaction domain) to suppress MSP-58-driven transformation [1].
• Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor [1].
• The nuclear MicroSpherule protein 58 is a novel RNA-binding protein that interacts with fragile X mental retardation protein in polyribosomal mRNPs from neurons [2].
• Interestingly, confocal microscopic analyses revealed the co-localization of MCRS1, Mi-2beta, RFP, and the rRNA transcription factor UBF in the nucleoli [3].
• Taken together, these findings delineate a network of regulatory signaling pathways that converges on MSP58/Daxx interaction, causally associating Daxx nucleolus targeting with its transcriptional activation function [4].

Biological context of MCRS1

• p78/MCRS1 forms a complex with centrosomal protein Nde1 and is essential for cell viability [5].
• Our findings suggest that MCRS2 might be a linker between telomere maintenance and cell-cycle regulation [6].
• The mouse MSP58 homolog has 97% amino acid similarity to human MSP58, but no MSP58 homolog was found in the yeast genome [7].
• High-frequency, reversible insertion/deletion frameshift mutations lead to selective phase variation in P78 expression, whereas the putative nucleotide-binding protein, P63, encoded by the most 5' gene of the operon, is continually expressed [8].

Anatomical context of MCRS1

• DIPA, which can localize to the centrosome, associates with p78/MCRS1/MSP58 and acts as a repressor of gene transcription [9].
• Moreover, immunofluorescence analysis unequivocally demonstrated that MSP58 overexpression results in a translocation of Daxx to the enlarged nucleoli in COS-1 or 293 cells, whereas Daxx exhibited a diffuse nuclear pattern in HeLa cells [4].
• When the MSP58 protein was overexpressed in COS-7 cells, the nucleolus became irregularly enlarged, which suggests that MSP58 may affect the size and shape of the nucleolus [7].
• We also show that MSP58, similar to FMRP, is present on polyribosomes prepared from synaptoneurosomes and that it behaves as an RNA-binding protein with a high affinity to the G-quartet structure [2].
• However, in neurons but not in glial cells, MSP58 is also present in the cytoplasmic compartment, as well as in neurites, where it co-localizes with FMRP [2].

Associations of MCRS1 with chemical compounds

• Anti-MSP58 Ig labeled nucleolar 'caps' when HeLa cells were treated with actinomycin D [7].
• Its C-terminal disulfide bridge renders P78 significantly more stable than P39 to thermal denaturation or denaturation by urea [10].
• The 3' distal gene encoding P78, a known surface-exposed antigen and the proposed substrate-binding lipoprotein of the transporter, is subject to localized hypermutation in a short homopolymeric tract of adenine residues located in the N-terminal coding region of the mature product [8].
• These fluctuations are caused by a non-constant input rate of E2 which may be due to changing ethanol concentrations in the reservoir of the MCRS [11].
• PURPOSE: The aim of our study was to investigate the high fluctuations of Estradiol (E2) plasma levels transdermally delivered in postmenopausal women by a commercially available membrane controlled reservoir system (MCRS) [11].

Physical interactions of MCRS1

• MCRS2 interacts with LPTS/PinX1 in vitro, in vivo and colocalizes with LPTS/PinX1 in cells [6].

Regulatory relationships of MCRS1

• MCRS2 and its amino terminus inhibit telomerase activity in vitro and long-term overexpression of MCRS2 in SMMC-7721 cells results in a gradual and progressive shortening of telomeres [6].

Other interactions of MCRS1

• We also found that MCRS1, Mi-2beta, and RFP were associated with rDNA using a chromatin immunoprecipitation assay [3].
• Human MCRS2, a cell-cycle-dependent protein, associates with LPTS/PinX1 and reduces the telomere length [6].
• The expression of MCRS2 protein is cell-cycle dependent, accumulating in the very early S phase [6].
• Binding of MSP58 to PTEN results in the suppression of MSP58-mediated transformation [12].

Analytical, diagnostic and therapeutic context of MCRS1

• Yeast two-hybrid assays revealed that MCRS1 bound to the ATPase/helicase region of Mi-2beta and the coiled-coil region of RFP [3].
• In cell cultures, we found that MSP58 is predominantly present in the nucleus where it interacts with the nuclear isoform of FMRP [2].
• Four linear, immunodominant epitopes corresponding to amino acids 91-105 (P78), 1-15 (P73), 8-22 (P74), and 34-48 (P75) of JE virus core proteins were identified by employing an enzyme-linked immunosorbent assay (ELISA), using high-titered immune sera from JE-vaccinated children [13].

References