The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms.
Transcription factor NF-kappa B (p50/p65) is generally localized to the cytoplasm by its inhibitor I kappa B. Overproduced I kappa B, free from NF-kappa B, is rapidly degraded. Overexpression of p65 increases endogenous I kappa B protein in both carcinoma and lymphoid cells by two mechanisms: protein stabilization and increased transcription of I kappa B mRNA. In contrast, p65 delta, a naturally occurring splice variant, fails to markedly augment I kappa B protein levels. Both overexpressed p65 and coexpressed p50 are cytoplasmic, whereas p65 delta is partly nuclear, indicating that the I kappa B induced by p65 can maintain NF-kappa B in the cytoplasm. Thus, p65 and I kappa B are linked in an autoregulatory loop, ensuring that NF-kappa B is held in the cytoplasm until cells are specifically induced to translocate it to the nucleus.
Scott
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ML
Rockefeller University, New York, New York 10021.
Fujita
T
T
Liou
H C
HC
Nolan
G P
GP
Baltimore
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D
D016475:3T3 Cells; D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005246:Feedback; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006706:Homeostasis; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins / Q000378:metabolism; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012190:Retroviridae; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009687:Nuclear Proteins; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D012333:RNA, Messenger; C497594:Relb protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051841:Transcription Factor RelB