NF-kappa B1 can inhibit v-Abl-induced lymphoid transformation by functioning as a negative regulator of cyclin D1 expression
Details
Publication Year 2002-08, Volume 22, Issue #15, Page 5563-5574
Journal Title
MOLECULAR AND CELLULAR BIOLOGY
Publication Type
Journal Article
Abstract
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 cycIin 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.
Publisher
AMER SOC MICROBIOLOGY
Keywords
NF-KAPPA-B; MURINE LEUKEMIA-VIRUS; TYROSINE KINASE; TRANSCRIPTION FACTORS; MICE LACKING; DEPENDENT REGULATION; TRANSGENIC MICE; CELLS; ACTIVATION; LYMPHOCYTES
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Creation Date: 2002-08-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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