Disease relevance of CSTF2

• The first 60 nucleotides of the major element have 68% identity to the negative regulatory element of HPV-16, and these elements bind the same cellular proteins, CstF-64, U2AF(65), and HuR [1].

High impact information on CSTF2

• Using a yeast two-hybrid screen to identify factors that interact with the polyadenylation factor CstF-64, we uncovered an interaction with the transcriptional coactivator PC4 [2].
• To extend this observation, we disrupted the endogenous CstF-64 gene in the B cell line DT40 and replaced it with a regulatable transgene [3].
• Strikingly, a 10-fold decrease in CstF-64 concentration did not markedly affect cell growth but specifically and dramatically reduced accumulation of IgM heavy chain mRNA [3].
• CstF 64 kDa and CPSF 100 kDa were distributed in a fibrogranular pattern in the nucleoplasm and, in addition, were concentrated in 1-4 bright foci [4].
• In CstF-64, a small region, highly conserved in metazoa, is responsible for interactions with two proteins, CstF-77 and symplekin, a nuclear protein of previously unknown function [5].

Biological context of CSTF2

• By microscopic fluorescence resonance energy transfer, we show that labeled DDX1 resides within a Förster distance of 10 nm of labeled CstF-64 protein in both the nucleoplasm and within cleavage bodies [6].
• Our results indicate that CstF-64 plays unexpected roles in regulating gene expression and cell growth in B cells [3].
• Although inhibitors of RNA transcription had no effect on DDX1 bodies or cleavage bodies, inhibitors of DNA replication resulted in loss of CstF-64-containing cleavage bodies [7].
• Here, we report that whereas DDX1 bodies, CBs and gems are present throughout interphase, CPSF-100-containing cleavage bodies are predominantly found during S and G2 phases, whereas CstF-64-containing cleavage bodies are primarily observed during S phase [7].
• CstF-64 (cleavage stimulation factor-64), a major regulatory protein of polyadenylation, is absent during male meiosis [8].

Anatomical context of CSTF2

• The RNA 3' cleavage factors CstF 64 kDa and CPSF 100 kDa are concentrated in nuclear domains closely associated with coiled bodies and newly synthesized RNA [4].
• The concentration of one CstF subunit (CstF-64) increases during activation of B cells, and this is sufficient to switch IgM heavy chain mRNA expression from membrane-bound form to secreted form [3].

Associations of CSTF2 with chemical compounds

• A striking effect on nuclear structures was observed with latrunculin B, an inhibitor of actin polymerization, resulting in the formation of needlelike nuclear spicules made up of CstF-64, CPSF-100, RNA, and RNA polymerase II [7].
• Changing Pro-41 to a serine residue in the CstF-64 RBD did not affect its affinity for poly(U)(18), but changes in amino acids downstream of the C-terminal alpha-helical region decreased affinity towards poly(U)(18) [8].

Physical interactions of CSTF2

• Coimmunoprecipitation analysis indicates that a proportion of CstF-64 protein resides in the same complex as DDX1 [6].
• HSF1 also complexes in a stress-induced manner with the 3' processing factor CstF-64 [9].

Regulatory relationships of CSTF2

• CstF-64 expression was upregulated by IFN-alpha at the protein, but not at the mRNA level [10].

Other interactions of CSTF2

• However, CstF-64 had a higher affinity for poly(U)(18) than tauCstF-64, whereas it had a lower affinity for poly(GU)(9) [8].
• Moreover, HCMV infection of HFFs increased the abundance of the PA cleavage stimulatory factor CstF-64, the potent splicing suppressor PTB, and the hypophosphorylated form of the splicing factor SF2 at 4 h postinfection [11].
• Moreover, the protein was found to localize in 1-6 subnuclear domains where PML and CstF64 proteins were also identified [12].
• Two IFN-alpha-inducible proteins, soluble N-ethylmaleimide-sensitive factor attachment protein alpha (alpha-SNAP) and cleavage stimulation factor-64 (CstF-64) previously not described in this context, were identified [10].

References