RGD Reference Report - Adhesion-dependent Skp2 transcription requires selenocysteine tRNA gene transcription-activating factor (STAF). - Rat Genome Database

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Adhesion-dependent Skp2 transcription requires selenocysteine tRNA gene transcription-activating factor (STAF).

Authors: Hernandez-Negrete, I  Sala-Newby, GB  Perl, A  Kunkel, GR  Newby, AC  Bond, M 
Citation: Hernandez-Negrete I, etal., Biochem J. 2011 May 15;436(1):133-43. doi: 10.1042/BJ20101798.
RGD ID: 9743924
Pubmed: PMID:21352097   (View Abstract at PubMed)
PMCID: PMC3105252   (View Article at PubMed Central)
DOI: DOI:10.1042/BJ20101798   (Journal Full-text)

Cell adhesion is essential for cell cycle progression in most normal cells. Loss of adhesion dependence is a hallmark of cellular transformation. The F-box protein Skp2 (S-phase kinase-associated protein 2) controls G(1)-S-phase progression and is subject to adhesion-dependent transcriptional regulation, although the mechanisms are poorly understood. We identify two cross-species conserved binding elements for the STAF (selenocysteine tRNA gene transcription-activating factor) in the Skp2 promoter that are essential for Skp2 promoter activity. Endogenous STAF specifically binds these elements in EMSA (electrophoretic mobility-shift assay) and ChIP (chromatin immunoprecipitation) analysis. STAF is sufficient and necessary for Skp2 promoter activity since exogenous STAF activates promoter activity and expression and STAF siRNA (small interfering RNA) inhibits Skp2 promoter activity, mRNA and protein expression and cell proliferation. Furthermore, ectopic Skp2 expression completely reverses the inhibitory effects of STAF silencing on proliferation. Importantly, STAF expression and binding to the Skp2 promoter is adhesion-dependent and associated with adhesion-dependent Skp2 expression in non-transformed cells. Ectopic STAF rescues Skp2 expression in suspension cells. Taken together, these results demonstrate that STAF is essential and sufficient for Skp2 promoter activity and plays a role in the adhesion-dependent expression of Skp2 and ultimately cell proliferation.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Zfp143Ratpositive regulation of smooth muscle cell proliferation  IMP  RGD 
Zfp143Ratpositive regulation of transcription by RNA polymerase II  IMP  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Zfp143Ratchromatin binding  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Zfp143  (zinc finger protein 143)


Additional Information