Disease relevance of Ubtf

• Cardiac hypertrophy in vivo is associated with increased expression of the ribosomal gene transcription factor UBF [1].

High impact information on Ubtf

• ERK phosphorylation of the HMG boxes of UBF, an RNA polymerase I factor essential for transcription enhancement, was shown to directly regulate elongation by inducing the remodeling of ribosomal gene chromatin [2].
• Chromatin immunoprecipitation assays demonstrate that methylation of the cytosine at -133 inhibits binding of the transcription factor UBF to nucleosomal rDNA, thereby preventing initiation complex formation [3].
• The difference in transcriptional activity between UBF1 and UBF2 is due to their different binding to the ribosomal gene promoter and enhancer [4].
• We show by a variety of different experimental approaches, such as immunoprecipitation, glycerol gradient sedimentation, affinity chromatography and protein blotting, that UBF physically associates with Pol I [5].
• The nucleolar transcription factor UBF consists of two proteins, UBF1 and UBF2, which originate by alternative splicing [4].

Biological context of Ubtf

• Activation of UBF1 requires its phosphorylation [6].
• Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase [6].
• Thus, mTOR plays a critical role in the regulation of ribosome biogenesis via a mechanism that requires S6K1 activation and phosphorylation of UBF [7].
• Pescadillo (PES1) and the upstream binding factor (UBF1) play a role in ribosome biogenesis, which regulates cell size, an important component of cell proliferation [8].
• After germinal vesicle breakdown, the RNA pol I complex disassembles in a step-wise manner from chromosomes, while UBF remains associated with chromosomes until late prometaphase I [9].

Anatomical context of Ubtf

• In contrast, PES1 and UBF1 can transform mouse embryo fibroblasts that have high levels of endogenous IRS-1 and are not prone to differentiation [8].
• We have investigated the effects of PES1 and UBF1 on the growth and differentiation of cell lines derived from 32D cells, an interleukin-3 (IL-3)-dependent murine myeloid cell line [8].
• 32D IGF-IR cells expressing PES1 or UBF1 differentiate into granulocytes like their parental cells [8].
• We show that rDNA transcription, rRNA synthesis and UBF expression in left ventricular myocytes isolated from mice 1-6 weeks following transverse aortic constriction were significantly increased (2.5-3.5-fold) compared to the levels in myocytes from the left ventricle of sham-operated mice [1].
• To assess the role of acetylation in regulation of UBF activity, we have established an NIH3T3 cell line that inducibly overexpresses HDAC1 [10].

Associations of Ubtf with chemical compounds

• NDH II migrated out of the nucleolus after administration of 0.05 microg/ml actinomycin D, while nucleolin and the upstream binding factor (UBF) remained there [11].
• Phosphorylation occurs on a number of UBF1 peptides, most prominently on the highly acidic, serine-rich C terminus [12].

Physical interactions of Ubtf

• In myeloid cells (but not in mouse embryo fibroblasts) IRS-1 signaling stabilizes the levels of UBF1 protein [12].

Other interactions of Ubtf

• mTOR-dependent regulation of ribosomal gene transcription requires S6K1 and is mediated by phosphorylation of the carboxy-terminal activation domain of the nucleolar transcription factor UBF [7].
• Regulation of upstream binding factor 1 activity by insulin-like growth factor I receptor signaling [12].

Analytical, diagnostic and therapeutic context of Ubtf

• These findings demonstrate that IGF-IR signaling can increase the activity of UBF1 and transcription from the rDNA promoter, providing one explanation for the reported effects of the IGF/IRS-1 axis on cell and body size in animals and cells in culture [12].
• Nuclear run-on assays and Northern blot analyses demonstrated that the UBF gene was a primary response gene, exhibiting characteristics similar to those of c-myc and SRF [13].

References