Regulation of the Transcription Factor UBF by CHP

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DESCRIPTION (provided by applicant) Calcineurin homologous protein, CHP, is a Ca2+-binding protein with diverse functions, including regulation of ion exchanger and calcineurin activities and constitutive vesicular transport. We have recently found that CHP is localized to the nuclear envelope and that overexpression of CHP inhibits cell proliferation. Upstream binding factor, UBF, is a necessary component of the transcription initiation complex of RNA polymerase I (P01 I) that functions to transcribe nuclear rDNA genes. Thus UBF is a key player in ribosome biosynthesis and cell proliferation. We have evidence demonstrating a novel in vivo interaction between CHP and UBF that is Ca2+-sensitive. This proposal will investigate the hypothesis that the interaction between CHP and UBF regulates UBF function, and is comprised of two primary Aims: 1) Investigate the regulated association of CHP with UBF, and 2) Determine the functional significance of the interaction of CHP with UBF. Aim 1 determines whether UBF binds directly to CHP and, if so, whether it is Ca2+-dependent, and investigates the regulated distribution of CHP and UBF in vivo. Aim 2 investigates whether the abundance, Ca2+ binding, and membrane association of CHP regulate UBF modifications and/or UBF-mediated rDNA transcription. Results of these experiments will advance our knowledge of how CHP and UBF are independently regulated as well as how their interaction regulates UBF function.