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Effects of Altered Expression and Localization of Cyclophilin A on Differentiation of p19 Embryonic Carcinoma Cells

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Abstract

1.The retinoblastoma susceptibility gene product, p105Rb (RB), is an important regulator in the control of cell proliferation, differentiation, and apoptosis. Several cellular factors that complex with RB and exert their cellular regulatory functions have been identified, such as the RB:cyclophilin A (CypA) complex.

2.CypA is a cytoplasmic immunophilin and known for its involvement in T-cell differentiation and proliferation. Although CypA has a pivotal role in the immune response, its function in other signaling pathways is largely unknown.

3.In this study, we used a model of neuronal differentiation to demonstrate that the nuclear translocation of CypA, the appearance of hypophosphorylated RB and the enhancement of RB: CypA complex formation correlates with retinoic acid induced neuronal differentiation.

4.Inhibition of CypA expression results in repression of both the hypophosphorylated RB and the neuron-specific differentiation marker, class III β tubulin.

5.The evidence of enriched CypA and colocalization of RB with CypA in the nucleus of primary adult sensory neurons substantiated the important event of RB-mediated neuronal differentiation of p19 EC cells.

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Authors and Affiliations

  1. Dental Research Institute, UCLA School of Dentistry, Los Angeles, California, USA

    Robert Chiu, Osvaldo Rey, Jun Song & Shen Pang

  2. Department of Surgery/Oncology, UCLA School of Medicine, Los Angeles, California, USA

    Robert Chiu

  3. Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, USA

    Robert Chiu

  4. Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA

    Osvaldo Rey

  5. Department of Pathology & Laboratory Medicine, UCLA School of Medicine, Los Angeles, California, USA

    Jun-Qi Zheng & Jeffery L. Twiss

  6. BioResource Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305, Japan

    Kazunari K. Yokoyama

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  1. Robert Chiu
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Correspondence to Robert Chiu.

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Chiu, R., Rey, O., Zheng, JQ. et al. Effects of Altered Expression and Localization of Cyclophilin A on Differentiation of p19 Embryonic Carcinoma Cells. Cell Mol Neurobiol 23, 929–943 (2003). https://doi.org/10.1023/B:CEMN.0000005321.11544.cc

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