High impact information on NCBP1

• Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20 [1].
• Consistent with the dependence of NMD on translation, the NMD of CBP80-bound mRNA is blocked by cycloheximide or suppressor tRNA [1].
• Polysome profiles indicate that CBP80-bound mRNAs are translated less efficiently than their eIF4E-bound counterparts [2].
• hnRNP F was identified in a screen for proteins that interact with human CBP80 and CBP20, the components of the nuclear cap-binding complex (CBC) [3].
• The CBC-mediated inhibition of PARN was cap-independent, and in keeping with this, the CBP80 subunit alone inhibited PARN [4].

Biological context of NCBP1

• Here, we provide evidence that CBP80 augments the efficiency of NMD but not of Staufen1 (Stau1)-mediated mRNA decay (SMD) [5].
• In vertebrates, a nuclear cap-binding complex (CBC) formed by two cap- binding proteins, CBP20 and CBP80, is involved in several steps of RNA metabolism, including pre-mRNA splicing and nuclear export of some RNA polymerase II-transcribed U snRNAs [6].
• S6 kinase may directly target the CBC in vivo as it can phosphorylate the 80-kDa subunit of the CBC, CBP80, at residues that are subject to a growth factor-dependent and rapamycin-sensitive phosphorylation in vivo [7].
• We have previously identified and purified an 80kD Nuclear Cap Binding Protein (NCBP) from a HeLa cell nuclear extract, which could possibly mediate these nuclear activities [8].
• Transfection experiments demonstrated that the epitope-tagged NCBP, transiently expressed in HeLa cells, was localized exclusively in the nucleoplasm [8].

Anatomical context of NCBP1

• As a candidate for the factor involved in these nuclear events we have previously purified an 80 kDa nuclear cap binding protein (NCBP) from a HeLa cell nuclear extract and isolated its full-length cDNA [9].
• The soluble stimuli formlymethionyl-leucyl-phenylalanine and the low-molecular-weight complement fragment C5a both promote the dose-dependent release of NCBP from cytochalasin B-treated neutrophils in vitro [10].

Associations of NCBP1 with chemical compounds

• The CBC represents a 20- and 80-kDa heterodimer (the subunits independently referred to as CBP20 and CBP80, respectively) that binds the 7-methylguanosine cap on RNAs transcribed by RNA polymerase II [11].
• A complex with a small N-terminal deletion in CBP80 was crystallized in space group C2 with one complex per asymmetric unit [12].
• The extracellular discharge of NCBP induced by higher secretagogue is inhibited by prior exposure of neutrophils to the corticosteroids hydrocortisone and methylprednisolone and the nonsteroidal antiinflammatory agents indomethacin and ibuprofen [10].

Physical interactions of NCBP1

• CBP80 stabilizes the movement of the N-terminal loop of CBP20 and locks the CBC into a high affinity cap-binding state [13].
• We propose a model in which eIF4G serves to connect CBP80/20 with other initiation factors during the pioneer round of translation [14].

Other interactions of NCBP1

• The cap-bound conformation of CBP20 is stabilized by an intricate network of interactions both to the ligand and within the subunit, as well as new interactions of the CBP20 N-terminal tail with the large subunit CBP80 [15].
• Here, we present evidence that eIF4G and the large subunit of the nuclear cap-binding complex, CBP80, share a common origin and domain structure [16].
• We showed that CBC, via its 80-kDa subunit (CBP80), inhibited PARN, suggesting that CBC can regulate mRNA deadenylation [4].

Analytical, diagnostic and therapeutic context of NCBP1

• Here, the engineering and crystallization of two variant CBCs with deletions in CBP80 which do not affect function are described [12].

References