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PMID: 10490645 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Regulation of RelA subcellular localization by a putative nuclear export signal and p50.

Molecular and cellular biology ·Vol. 19 ·No. 10 ·1999-10-00 ·Pages 7088-95

Harhaj EW, Sun SC

Abstract

Nuclear factor kappaB (NF-kappaB) represents a family of dimeric DNA binding proteins, the pleotropic form of which is a heterodimer composed of RelA and p50 subunits. The biological activity of NF-kappaB is controlled through its subcellular localization. Inactive NF-kappaB is sequestered in the cytoplasm by physical interaction with an inhibitor, IkappaBalpha. Signal-mediated IkappaBalpha degradation triggers the release and subsequent nuclear translocation of NF-kappaB. It remains unknown whether the NF-kappaB shuttling between the cytoplasm and nucleus is subjected to additional steps of regulation. In this study, we demonstrated that the RelA subunit of NF-kappaB exhibits strong cytoplasmic localization activity even in the absence of IkappaBalpha inhibition. The cytoplasmic distribution of RelA is largely mediated by a leucine-rich sequence homologous to the recently characterized nuclear export signal (NES). This putative NES is both required and sufficient to mediate cytoplasmic localization of RelA as well as that of heterologous proteins. Furthermore, the cytoplasmic distribution of RelA is sensitive to a nuclear export inhibitor, leptomycin B, suggesting that RelA undergoes continuous nuclear export. Interestingly, expression of p50 prevents the cytoplasmic expression of RelA, leading to the nuclear accumulation of both RelA and p50. Together, these results suggest that the nuclear and cytoplasmic shuttling of RelA is regulated by both an intrinsic NES-like sequence and the p50 subunit of NF-kappaB.

MeSH Terms
Amino Acid Motifs Amino Acid Sequence Biological Transport Carrier Proteins/metabolism Cell Compartmentation Cell Nucleus/metabolism Cytoplasm/metabolism Fatty Acids, Unsaturated/pharmacology Karyopherins Molecular Sequence Data NF-kappa B/isolation & purification,metabolism NF-kappa B p50 Subunit Receptors, Cytoplasmic and Nuclear Transcription Factor RelA
Chemicals
Carrier Proteins Fatty Acids, Unsaturated Karyopherins NF-kappa B NF-kappa B p50 Subunit Receptors, Cytoplasmic and Nuclear Transcription Factor RelA exportin 1 protein leptomycin B
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Harhaj E W
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Sun S C
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.10.7088
Published
1999-10-00
Pages
7088-95
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84703
Subset
IM
Grants
NCI NIH HHS · R01 CA068471 · United States
NCI NIH HHS · 1 R01 CA68471 · United States
NCI NIH HHS · 5 T32 CA6039-5 · United States
External Links
PubMed source DOI: 10.1128/MCB.19.10.7088 PMC Full Text View journal details
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