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The p65 subunit of NF-κB regulates IκB by two distinct mechanisms

Scott, Martin L. and Fujita, Takashi and Liou, Hsiou-Chi and Nolan, Garry P. and Baltimore, David (1993) The p65 subunit of NF-κB regulates IκB by two distinct mechanisms. Genes and Development, 7 (7a). pp. 1266-1276. ISSN 0890-9369.

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Transcription factor NF-κB (p50/p65) is generally localized to the cytoplasm by its inhibitor IκB. Overproduced IκB, free from NF-κB, is rapidly degraded. Overexpression of p65 increases endogenous IκB protein in both carcinoma and lymphoid cells by two mechanisms: protein stabilization and increased transcription of IκB mRNA. In contrast, p65Δ, a naturally occurring splice variant, fails to markedly augment IκB protein levels. Both overexpressed p65 and coexpressed p50 are cytoplasmic, whereas p65Δ is partly nuclear, indicating that the IκB induced by p65 can maintain NF-κB in the cytoplasm. Thus, p65 and IκB are linked in an autoregulatory loop, ensuring that NF-κB is held in the cytoplasm until cells are specifically induced to translocate it to the nucleus.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1993 by Cold Spring Harbor Laboratory Press. Received March 22, 1993; revised version accepted April 20, 1993. We thank Warren Pear for the transient transfection protocol and cells used to generate retroviral stocks. We gratefully acknowledge Bruce Mayer, William Sha, and other members of the Baltimore laboratory for helpful comments on the manuscript. We also appreciate the use of the MFG retroviral vector provided by P. Robbins (University of Pittsburgh) and R. Mulligan (Whitehead Institute). This work was supported in part by grants from the American Cancer Society (M.L.S.) and Leukemia Society (G.P.N.). Other support was provided by the National Institutes of Health (GM 39458 and CA 51462). The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.
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American Cancer SocietyUNSPECIFIED
Leukemia Society of AmericaUNSPECIFIED
Subject Keywords:NF-κB; autoregulation; B-cell development
Issue or Number:7a
Record Number:CaltechAUTHORS:20200513-140848808
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103183
Deposited By: Tony Diaz
Deposited On:13 May 2020 22:24
Last Modified:13 May 2020 22:24

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