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Interaction of the retinoblastoma gene product, RB, with cyclophilin A negatively affects cyclosporin‐inhibited NFAT signaling
Author(s) -
Cui Yukun,
Mirkia Kirash,
Florence Fu YuHsieh,
Zhu Li,
Yokoyama Kazunari K.,
Chiu Robert
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10253
Subject(s) - cypa , nfat , jurkat cells , cyclophilin a , microbiology and biotechnology , biology , ionomycin , transcription factor , cell growth , chemistry , t cell , biochemistry , gene , intracellular , immunology , immune system
The retinoblastoma susceptibility gene product, p105Rb (RB), is generally believed to be an important regulator in the control of cell growth, differentiation, and apoptosis. Several cellular factors that form complexes with RB and exert their cellular regulatory functions have been identified, such as the newly identified RB:cyclophilin A (CypA) complex. The physical interactions between RB and CypA were demonstrated by glutathione S ‐transferase affinity matrix binding assays and immunoprecipitation, followed by Western blot analyses. The N‐terminal region of CypA mediated the interaction with RB, whereas the region upstream of the A‐pocket of RB was required for binding to CypA. Ectopic expression of RB into Jurkat cells partially blocks the function of cyclosporin (CsA) to inhibit nuclear factor for activation of T cell (NFAT) activation by phorbol ester (PMA) plus ionomycin A (IA), suggesting that RB may prevent CsA inhibition of T lymphocyte activation. These results are further evidenced by the effect of RB on both calcineurin (CN) and NFAT binding activity in vitro, suggesting that the interaction of RB with CypA interferes with the CsA:CypA complex and blocks CsA‐inhibited CN activity. These data reveal the functional link between RB and CypA and their involvement in T cell activation signaling. J. Cell. Biochem. 86: 630–641, 2002. © 2002 Wiley‐Liss, Inc.