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Increased p21 expression and complex formation with cyclin E/CDK2 in retinoid‐induced pre‐B lymphoma cell apoptosis
Author(s) -
Bao George C.,
Wang Jian-Guang,
Jong Ambrose
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.05.052
Subject(s) - cyclin dependent kinase 2 , cyclin dependent kinase , cyclin e , cancer research , retinoic acid , microbiology and biotechnology , apoptosis , cyclin a , cyclin a2 , cyclin d , biology , cyclin , chemistry , kinase , cell cycle , protein kinase a , biochemistry , cell culture , genetics
Cip/Kip family protein p21, a cyclin‐dependent kinase (CDK) inhibitor, is directly transactivated by retinoic acid receptor alpha (RARα) upon retinoic acid (RA):RARα binding. Yet the role of p21 upregulation by RA in lymphoma cells remains unknown. Here, we show that, in human pre‐B lymphoma Nalm6 cells, RA‐induced proliferation inhibition results from massive cell death characterized by apoptosis. Upregulated p21 by RA accompanies caspase‐3 activation and precedes the occurrence of apoptosis. p21 induction leads to increased p21 complex formation with cyclin E/CDK2, which occurs when cyclin E and CDK2 levels remain constant. CDK2 can alternatively promote apoptosis, but the mechanisms remain unknown. Data presented here suggest a novel RA‐signaling, by which RA‐induced p21 induction and complex formation with cyclin E/CDK2 diverts CDK2 function from normally driving proliferation to alternatively promoting apoptosis.