Nuclear-localized Calcineurin Homologous Protein CHP1 Interacts with Upstream Binding Factor and Inhibits Ribosomal RNA Synthesis

Department of Cell and Tissue Biology, University of California, San Francisco, California 94143, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 11/2010; 285(47):36260-6. DOI: 10.1074/jbc.M110.165555
Source: PubMed

ABSTRACT Calcineurin homologous protein 1 (CHP1) is a widely expressed, 22-kDa myristoylated EF-hand Ca(2+)-binding protein that shares a high degree of similarity with the regulatory B subunit of calcineurin (65%) and with calmodulin (59%). CHP1 localizes to the plasma membrane, the Golgi apparatus, and the nucleus and functions to regulate trafficking of early secretory vesicles, activation of T cells, and expression and transport of the Na-H exchanger NHE1. Although CHP1 contains nuclear export signals, whether its nuclear and cytoplasmic localization is regulated and has distinct functions remain unknown. We show that CHP1 is predominantly in the nucleus in quiescent fibroblasts, is translocated to cytoplasmic compartments with growth medium, and that translocation is inhibited by mutations in the nuclear export motifs. In a screen for proteins co-precipitating with CHP1 in quiescent cells we identified the upstream binding factor UBF, a DNA-binding protein and component of the RNA polymerase I complex regulating RNA synthesis. The CHP1-UBF interaction is restricted to the nucleus and inhibited by Ca(2+). Nuclear retention of CHP1 attenuates the abundance of UBF in the nucleolus and inhibits RNA synthesis when quiescent cells are transferred to growth medium. These data show UBF as a newly identified CHP1-binding protein and regulation of RNA synthesis as a newly identified function for nuclear-localized CHP1, which is distinct from CHP1 functions in the cytosol.

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    • "Calcium binding protein p22 (Chp), which belongs to the EF-hand superfamily of Ca(2+) binding proteins, may act by transducing cellular Ca(2+) signals to downstream effectors in many cell types [13]. It is also known to be an endogenous inhibitor of calcineurin activity [14] and thus inactivates the T cells of the immune system. Prehypertension showed the symptoms of dizziness, headache, anxiety, and irritability [15]. "
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    • "Although it is well established that the dephosphorylation of Crz1p by calcineurin leads to its nuclear translocation (Stathopoulos-Gerontides et al., 1999), there are no reports of the nuclear localization of calcineurin B in the yeasts or filamentous fungi. Nuclear localization of a calcineurin B homologous protein (CHP1) has been reported (Nagita et al., 2003, Jiménez-Vidal et al., 2010). We could not identify any potential NLS sequence in the A. fumigatus CnaB and it is possible that CnaB may translocate into the nucleus with CnaA and CrzA. "
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