Disease relevance of RUVBL1

• Regulation of COX-2 transcription in a colon cancer cell line by Pontin52/TIP49a [1].
• Interestingly, we detected a high level of autoantibodies against TIP49 in sera of patients with autoimmune diseases such as polymyositis/dermatomyositis and autoimmune hepatitis [2].
• At least, TIP49a has been suggested to act as an autoantigen in some patients with autoimmune diseases [3].

High impact information on RUVBL1

• We suggest that TIP49 is an important cofactor in beta-catenin/TCF gene regulation in normal and neoplastic cells, likely functioning in chromatin remodeling [4].
• In this study, we isolated a new TIP49a-related gene, termed TIP49b, from human and yeast cells [5].
• Like TIP49a, TIP49b was abundantly expressed in the testis and thymus [5].
• We extended our analysis of TIP49 to show that it also binds to the E2F1 transactivation domain and modulates both transforming and apoptotic activities [6].
• Interestingly, TIP48 formed oligomers in the presence of adenine nucleotides, whilst TIP49 did not [7].

Biological context of RUVBL1

• The TIP49b/RUVBL2 open reading frame encodes a protein of 463 amino acids, showing 43% identity with the RUVBL1 protein [8].
• Analysis of the nucleotide sequences revealed that ECP-51 and ECP-54 are homologous (44.2% amino acid identity) and contain ATP-binding sites [9].
• TIP48/TIP49 complex formation resulted in synergistic increase in ATPase activity but ATP hydrolysis was not stimulated in the presence of single-stranded, double-stranded or four-way junction DNA and no DNA helicase or branch migration activity could be detected [7].
• These results are consistent with our previous results from tissue distribution analysis for of TIP49 proteins [3].
• Chromosome mapping and expression of human tip49 family genes [3].

Anatomical context of RUVBL1

• TIP49b/RUVBL2, like RUVBL1, was expressed ubiquitously in all human tissues examined and more strongly in testis [8].
• Confocal immunoflourescence microscopy reveals that RUVBL1/TIP49a was present not only in the nucleus, as expected, but was also concentrated at the centrosome and at the mitotic spindle in colocalization with tubulin [10].
• Identification and characterization of the ubiquitously occurring nuclear matrix protein NMP 238 [11].

Associations of RUVBL1 with chemical compounds

• We recovered and identified RUVBL1/TIP49a as a tubulin-binding protein from Triton X-100 lysates of U937 promonocytic cells by protein affinity chromatography and tryptic peptide microsequencing [10].
• Three-dimensional reconstruction at 20 A resolution revealed that the TIP48/TIP49 complex consisted of two stacked hexameric rings with C6 symmetry [7].
• Moreover, glycerol gradient analysis demonstrated that TIP49 is present in a macromolecular complex in nuclear extracts [2].
• Using histidine-tagged TBP for affinity-purification of TBP-bound proteins, we isolated a 49-kD protein termed TBP-interacting protein 49 (TIP49) from rat liver nuclear extracts [12].
• RUVBL1/TIP49a/Pontin52 is a recently identified multi-functional protein with 2 ATP binding (WALKER) sites, which is essential for cell proliferation [10].

Physical interactions of RUVBL1

• The structure of the TIP48/TIP49 complex was examined by negative stain electron microscopy [7].

Other interactions of RUVBL1

• The interaction of ECP-51 and ECP-54 with the stomatin peptide and the localization to the nucleus and cytoplasm suggest an additional function for these proteins as chaperone components [9].
• Here we show that the regulation of the expression of this enzyme in a colon cancer cell line, and in patients, is associated with overexpression of the Wnt pathway-associated proteins, Pontin52/TIP49a and LEF-1 [1].
• RUVBL1 and PSA expression was further confirmed by real-time quantitative PCR, whose results paralleled the microarray data [13].
• TIP49, homologous to the bacterial DNA helicase RuvB, acts as an autoantigen in human [2].
• TBP-interacting protein 49 (TIP49) was originally identified as a TBP-binding protein, and two related proteins are encoded by individual genes, tip49a and b [3].

Analytical, diagnostic and therapeutic context of RUVBL1

• Immunoprecipitation analysis of the cell extracts indicated that TIP49 and TBP were present in an identical complex [12].
• Immunofluorescence analysis using anti-TIP49 antibody showed a typical dot-shaped nuclear staining pattern, suggesting that TIP49 is included in a macromolecular structure in the nucleus and may participate in nuclear events such as transcription and recombination [2].
• Consistent with the notion that tip49 family genes are essential for cell growth, Northern blot analysis demonstrated that both genes are expressed ubiquitously in human tissues [3].
• Expression, purification, crystallization and preliminary X-ray analysis of the human RuvB-like protein RuvBL1 [14].

References