UBTF

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Protein-coding gene in the species Homo sapiens

title: "UBTF" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/UBTF" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Upstream binding transcription factor (UBTF), or upstream binding factor (UBF), is a protein that in humans is encoded by the UBTF gene.

Gene

In humans, the UBTF gene encodes a 764 amino acid protein and is located on chromosome 17 at position q21.31. In mice, UBTF is found on chromosome 11 .

Structure

UBTF contains six high mobility group boxes (HMG-boxes) that allow it to bind to DNA. UBTF also contains a hyperacidic carboxy-terminal domain, which is required for transcription activation, and a helix-gap-helix dimersation motif (as UBTF is thought to often act as a dimer).

In humans, alternative splicing can give rise to either the UBTF1 or UBTF2 isoform which are 97 kD and 94 kD in mass, respectively UBTF2 lacks exon 8 of the larger UBTF1 isoform which encodes a portion of HMG Box 2.

Function

UBTF is a transcription factor required for expression of the 18S, 5.8S, and 28S ribosomal RNAs, along with SL1 (a complex of TBP (MIM 600075) and three TBP-associated factors or 'TAFs').

UBTF is a nucleolar phosphoprotein with both DNA binding and transactivation domains. Sequence-specific DNA binding to the core and upstream control elements of the human rRNA promoter is mediated through several HMG boxes. [supplied by OMIM]

In vertebrates, UBTF plays a crucial role in maintaining rDNA chromatin in a euchromatic state. Consequently, UBTF binding is one of the characteristics of euchromatic, transcriptionally active rDNA repeats.

UBTF2 has been found to regulate mRNA transcription by RNA Polymerase II.

Clinical significance

UBTF may have a role in cancer. Increased UBF binding to rDNA has been observed in cancer cells and is associated with elevated rDNA transcription and tumor cell survival. Supporting this, it was found that cisplatin, a chemotherapy drug, can displace UBTF from rDNA, causing a reduction in rRNA synthesis and subsequent p53-independent apoptosis.

Additionally, UBTF has been found to facilitate melanoma by promoting GIT1 expression which, in turn, activates MEK1/2-ERK1/2 signaling pathways.

UBTF may also be important to neurological functioning. A de novo gain-of-function mutation to UBTF (c.628GA) has been found to cause developmental neuroregression. This mutation replaces glutamic acid with lysine at position 210 of the polypeptide chain (p.Glu210Lys) which results in a stronger UBTF interaction with DNA. In 2022, another likely pathogenic variant (Gln203Arg) was identified in a proband with severe early-onset developmental delay..

Interactions

UBTF has been shown to interact with:

References

References

  1. (May 1997). "Molecular cloning of the RNA polymerase I transcription factor hUBF/NOR-90 (UBTF) gene and localization to 17q21.3 by fluorescence in situ hybridization and radiation hybrid mapping". Genomics.
  2. "Entrez Gene: UBTF upstream binding transcription factor, RNA polymerase I".
  3. (Dec 1995). "Localization of the Human RNA Polymerase I Transcription Factor Gene (UBTF) to the D17S183 Locus on Chromosome 17q21 and Construction of a Long-Range Restriction Map of the Region". Genomics.
  4. (Aug 2017). "Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood". American Journal of Human Genetics.
  5. (Feb 2015). "A novel role for the Pol I transcription factor UBTF in maintaining genome stability through the regulation of highly transcribed Pol II genes". Genome Res.
  6. (Jan 1994). "The HMG box-containing nucleolar transcription factor UBF interacts with a specific subunit of RNA polymerase I". EMBO J.
  7. (Sep 1988). "Functional cooperativity between transcription factors UBF1 and SL1 mediates human ribosomal RNA synthesis". Science.
  8. (Feb 2018). "A recurrent de novo missense mutation in UBTF causes developmental neuroregression". EMBO J.
  9. (Apr 1990). "Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins". Nature.
  10. (Aug 2009). "The role of UBF in regulating the structure and dynamics of transcriptionally active rDNA chromatin". Epigenetics.
  11. (Jan 2019). "Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation". Communications Biology.
  12. (Sep 2015). "Depletion of the cisplatin targeted HMGB-box factor UBF selectively induces p53-independent apoptotic death in transformed cells". Oncotarget.
  13. (Oct 2021). "UBTF facilitates melanoma progression via modulating MEK1/2-ERK1/2 signalling pathways by promoting GIT1 transcription". Cancer Cell International.
  14. (Aug 2017). "Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood". American Journal of Human Genetics.
  15. (Dec 2022). "A novel, likely pathogenic variant in UBTF-related neurodegeneration with brain atrophy is associated with a severe divergent neurodevelopmental phenotype". Molecular Genetics & Genomic Medicine.
  16. (July 1995). "Activation of mammalian ribosomal gene transcription requires phosphorylation of the nucleolar transcription factor UBF". Nucleic Acids Res..
  17. (October 2000). "Rb and p130 regulate RNA polymerase I transcription: Rb disrupts the interaction between UBF and SL-1". Oncogene.
  18. (November 2001). "Phosphorylation of UBF at serine 388 is required for interaction with RNA polymerase I and activation of rDNA transcription". Proc. Natl. Acad. Sci. U.S.A..
  19. (August 2000). "Repression of RNA polymerase I transcription by the tumor suppressor p53". Mol. Cell. Biol..
  20. (Dec 2002). "The cell cycle regulatory factor TAF1 stimulates ribosomal DNA transcription by binding to the activator UBF". Curr. Biol..

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