Effects of altered expression and localization of cyclophilin A on differentiation of p19 embryonic carcinoma cells

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...

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Published in:Cellular and molecular neurobiology 2003-12, Vol.23 (6), p.929-943
Main Authors: Chiu, Robert, Rey, Osvaldo, Zheng, Jun-Qi, Twiss, Jeffery L, Song, Jun, Pang, Shen, Yokoyama, Kazunari K
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - genetics
Cells, Cultured
Cyclophilin A - biosynthesis
Cyclophilin A - genetics
Cyclophilin A - metabolism
Cyclophilin A - physiology
Embryo, Mammalian
Embryonal Carcinoma Stem Cells
Ganglia, Spinal - cytology
Ganglia, Spinal - metabolism
Gene Expression Regulation, Developmental - physiology
Male
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Rats
Rats, Sprague-Dawley
Retinoblastoma Protein - genetics
Retinoblastoma Protein - metabolism
Tumor Cells, Cultured
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Summary: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 beta 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.
ISSN:0272-4340
DOI:10.1023/B:CEMN.0000005321.11544.cc