Open AccessNF-κB1 Can Inhibit v-Abl-Induced Lymphoid Transformation by Functioning as a Negative Regulator of Cyclin D1 Expression
Author(s) -
Yukio Nakamura,
Raelene J. Grumont,
Steve Gerondakis
Publication year - 2002
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.22.15.5563-5574.2002
Subject(s) - cyclin d1 , biology , cyclin d , cyclin a2 , cancer research , cyclin b , cyclin , nf κb , microbiology and biotechnology , cyclin a , cyclin dependent kinase complex , abl , regulator , cell cycle , signal transduction , cell , genetics , gene , tyrosine kinase
Mounting evidence implicates deregulated Rel/NF-kappaB signaling as a common feature of lymphoid malignancies. Despite the fact that they promote the survival and proliferation of normal lymphocytes, the underlying mechanisms by which various Rel/NF-kappaB proteins with different transcriptional regulatory capacities might facilitate transformation remain to be established. Here we show that the proliferation and tumorigenicity of Abelson murine leukemia virus (A-MuLV)-transformed pre-B cells are enhanced in the absence of NF-kappaB1 and that this coincides with elevated levels of cyclin D1. Support for a link between cyclin D1 expression and v-Abl transformation came from the finding that proliferation of transformed pre-B cells was reduced in the absence of cyclin D1, while enforced cyclin D1 expression increased the proliferation and tumorigenicity of wild-type transformants. A reduction in endogenous cyclin D1 levels that coincided with NF-kappaB1 transgene reversal of enhanced nfkb1(-/-) pre-B-cell transformation, coupled with NF-kappaB1 inhibition of v-Abl-induced kappaB-dependent murine cyclin D1 transcription, lends support to a model in which v-Abl-induced cyclin D1 transcription in transformed pre-B cells is controlled by Rel/NF-kappaB dimers with different activities.