Disease relevance of FBL

• This protein is expressed at high levels by a Friend virus-induced erythroleukemia of C57BL/6 (B6) origin, FBL, and has been shown to serve as an efficient tumor-specific rejection antigen in B6 mice [1].
• FBL -L reacted with leukemic cells in 8/9 cases of clinically recognized acute myeloid leukemia, including myeloid blast crisis of chronic granulocytic leukemia, 3/3 cases of chronic phase chronic myelogenous leukemia, and in 2/7 cases of clinically undifferentiated acute leukemia [2].
• Four hundred forty-seven women attending a breast clinic because of either suspicious lesions, anxiety about breast cancer, follow-up after the removal of a benign breast lesion, or a family history of breast cancer had a routine test for percentage of ferritin-bearing lymphocytes ( FBL ) in their peripheral blood [3].
• Autoantibodies specific against fibrillarin, a 34-kD nucleolar protein associated with U3-snRNP, are present in patients with systemic sclerosis (SSc) [4].
• While a hexapeptide sequence NH2 terminus of fibrillarin is shared with an Epstein-Barr virus-encoded nuclear antigen, the COOH-terminal region shares sequence homology with P40, the capsid protein encoded by herpes virus type 1 [4].

Psychiatry related information on FBL

• We show that a synthetic peptide R9 (GGRGRGGGF) with the RGG sequence present in human fibrillarin and fragile X mental retardation protein (FMRP) can be specifically methylated by rat brain extract [5].

High impact information on FBL

• We present the primary sequence of Xenopus U8, a fibrillarin-associated nucleolar snRNA, and examine its expression through oocyte development [6].
• The coiled body is a nuclear organelle that contains snRNPs involved in splicing, the non-snRNP splicing factor U2AF and the nucleolar protein fibrillarin [7].
• To understand the mechanisms involved in the induction of these autoantibodies, we prepared a series of human fibrillarin recombinant proteins covering the entire molecule and analyzed their interaction with the autoantibodies present in various connective tissue diseases [4].
• However, adoptively transferred envelope-specific T cells from immunized non-TG B6 mice mediated complete eradication of FBL tumor cells in TG mice, and did not induce detectable autoimmune damage to TG lymphoid tissues [1].
• In vitro assembly of an archaeal box C/D sRNP using recombinant core proteins L7, Nop56/58 and fibrillarin has yielded an RNA:protein enzyme that guides methylation from both the terminal box C/D core and internal C'/D' RNP complexes [8].

Biological context of FBL

• Fibrillarin methylation was strongest in the presence of the cytosolic fraction, followed by the ribosomal and then the nucleus fractions [9].
• Expression of fibrillarin reached a maximum in the first cell cycle and then dropped to a basic level in stimulated lymphocytes [10].
• This structure exhibited a pre-formed backbone geometry at the cofactor binding site similar to that when the cofactor is bound, suggesting that binding of Nop5p alone to fibrillarin is sufficient to stabilize the AdoMet-binding pocket [11].
• Protein pull-down experiments demonstrated that Nop56/58 self-dimerization and Nop56/58 dimerization with the core protein fibrillarin are mutually exclusive protein:protein interactions [12].
• The absence of nuclear transport did not affect the sequestration into daughter nuclei of components such as DNA, DNA topoisomerase I and the nucleolar protein fibrillarin that are carried through mitosis on chromosomes [13].

Anatomical context of FBL

• The survival of motor neurons (SMN) protein interacts with the snoRNP proteins fibrillarin and GAR1 [14].
• The data support other observations that nucleolin is a stabile structural protein at the ribosomal genes while fibrillarin may have a more specific functional role in nucleologenesis and ribosome production [10].
• Compared to nucleolin, the level of fibrillarin decreased more rapidly and more extensively in differentiating HL-60 cells [10].
• In addition, the fibrillarin- and nucleolin-derived peptides were used to detect elevated PRMT activity in homogenates of NGF-treated PC12 cells [15].
• METHODS: Nucleoli in monocytes were visualized using cytochemical procedures that detect RNA and characteristic nucleolar proteins, i.e. nucleophosmin, nucleolin, fibrillarin and AgNOR proteins, in peripheral blood smears [16].

Associations of FBL with chemical compounds

• SMN interaction requires the arginine- and glycine-rich domains of both fibrillarin and GAR1 and is defective in SMN mutants found in some SMA patients [14].
• The protein-arginine methyltransferase activities in the three fractions were analyzed using recombinant fibrillarin (a nucleolar RGG protein) as the methyl-accepting substrate [9].
• Structural and thermodynamic evidence for a stabilizing role of Nop5p in S-adenosyl-L-methionine binding to fibrillarin [11].
• Thus, fibrillarin dissociated from the nucleolar remnant at prophase of mitosis or following actinomycin D treatments after B23, but was found to be more prominent within the perichromosomal layer at metaphase, and earlier migrated to the reassembled nucleoli at telophase [17].
• The fucose-binding lectin from Lotus tetragonolobus ( FBL -L) has been previously shown to bind specifically to normal cells of the myeloid and monocytic lineages [2].

Physical interactions of FBL

• Very little SRP RNA was detected in fibrillar centers or the DFC of the nucleolus, as defined by the RNA polymerase I-specific upstream binding factor and the protein fibrillarin, respectively [18].

Co-localisations of FBL

• In early to middle M phase of the cell cycle, MPP10 colocalized with fibrillarin to chromosome surfaces [19].

Other interactions of FBL

• Coimmunoprecipitations demonstrate that the SMN complex associates with fibrillarin and with GAR1 in vivo [14].
• Coimmunoprecipitation experiments confirmed that p68 and fibrillarin can form complexes in cellular extracts, and deletion analysis identified regions in each protein responsible for mediating the interaction [20].
• Arginine methylation of recombinant murine fibrillarin by protein arginine methyltransferase [21].
• Double immunostaining with p14(ARF) and B23/nucleophosmin or fibrillarin antibodies using 3D microscopy revealed that p14(ARF) is located mainly in the granular component of the nucleolus. p14(ARF) was also found in distinct granular aggregates scattered throughout the nucleoplasm [22].
• To identify the structural elements responsible for these large conformational differences, we refined a crystal structure of Archaeoglobus fulgidus fibrillarin-Nop5p binary complex at 3.5 A [11].

Analytical, diagnostic and therapeutic context of FBL

• Our results of protease digestion, methylation competition reactions, and immunoblotting with a methylarginine-specific antibody all indicate that the methylation of fibrillarin is in the N-terminal GAR domain and arginyl residues are modified [21].
• In situ hybridization assays showed that the fibrillarin tagged by the elicited antibodies was colocalized with U3 snoRNP in the nucleolus in a clumpy manner and coprecipitated the U3 snoRNP [23].
• The recombinant fibrillarin tested by ELISA was recognized by the clumpy scleroderma serum from the majority of patients [23].
• Immunoprecipitation experiments using whole cell extracts of HeLa cells and cultured neurons revealed that abSMN coprecipitated small amounts of the U3 small nucleolar RNA (snoRNA) previously shown to be associated with fibrillarin in vivo [24].
• Results obtained from competitive inhibition radioimmunoassay and Western blot analyses with purified recombinant fusion proteins revealed that these autoantibodies react primarily with epitope(s) present in the NH2- (AA 1-80) and COOH-terminal (AA 276-321) domains of fibrillarin [4].

References