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_6 label "Selventa" provenance.
_5 value "However, coactivation of both signaling pathways led to a sixfold induction of cyclin D1. These observations are consistent with previous reports of cooperative regulation of cyclin D1 by RAS effector pathways and with the reported effects of the ERK mitogen-activated protein kinase pathway on cyclin D1 gene transcription and of AKT on cyclin D1 protein stabilization (1, 2, 13, 19). Activation of AKT alone had only a modest effect on p27Kip1 expression, consistent with previous observations that suggest that AKT activation reduces p27Kip1 expression by 50% (38). By contrast, activation of RAF alone led to significant repression of p27Kip1 expression, but this was not clearly manifest until 12 to 24 h after RAF activation. Strikingly, coactivation of RAF and AKT led to a rapid and profound repression of p27Kip1 expression that was clearly evident at 6 h and continued up to 24 h (Fig. 2A). It is noteworthy that the effects of RAF activation alone on cyclin D1 and p27Kip1 expression, especially at later time points, are likely enhanced due to activation of PI3'-kinase signaling through the release of autocrine growth factors such as HB-EGF (34, 58). The expression of p27Kip1 is reported to be under both transcriptional and posttranscriptional control (31, 38, 42, 54, 61). To investigate the mechanism(s) underlying the regulated expression of p27Kip1 by RAF and AKT, we assessed the effects of these protein kinases on KIP1 mRNA expression in 3T3-RA cells (Fig. 2B and C). Consistent with previous observations, activation of AKT alone led to a 50% reduction of KIP1 mRNA that was evident after 24 h (38)." provenance.
_5 wasQuotedFrom 15572689 provenance.
assertion hadPrimarySource 15572689 provenance.
large_corpus.bel title "BEL Framework Large Corpus Document" provenance.
large_corpus.bel description "Approximately 61,000 statements." provenance.
assertion wasDerivedFrom large_corpus.bel provenance.
assertion wasDerivedFrom _5 provenance.
large_corpus.bel authoredBy _6 provenance.
large_corpus.bel version "1.4" provenance.