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Molecular and Cellular Biology, August 2002, p. 5563-5574, Vol. 22, No. 15
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.15.5563-5574.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

NF-{kappa}B1 Can Inhibit v-Abl-Induced Lymphoid Transformation by Functioning as a Negative Regulator of Cyclin D1 Expression

Yukio Nakamura,{dagger}, Raelene J. Grumont, and Steve Gerondakis*

The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria 3050, Australia

Received 11 October 2001/ Returned for modification 30 November 2001/ Accepted 16 April 2002

Mounting evidence implicates deregulated Rel/NF-{kappa}B 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-{kappa}B 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-{kappa}B1 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-{kappa}B1 transgene reversal of enhanced nfkb1-/- pre-B-cell transformation, coupled with NF-{kappa}B1 inhibition of v-Abl-induced {kappa}B-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-{kappa}B dimers with different activities.


* Corresponding author. Mailing address: The Walter and Eliza Hall Institute of Medical Research. Post Office The Royal Melbourne Hospital, Victoria 3050, Australia. Phone: 61-3-93452 555. Fax: 61-3-9347 0852. E-mail: gerondakis {at}wehi.edu.au.

{dagger} Present address: Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.


Molecular and Cellular Biology, August 2002, p. 5563-5574, Vol. 22, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.15.5563-5574.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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