The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1

R. Tiedt, Boris A. Bartholdy, G. Matthias, J. W. Newell, P. Matthias

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

The transcriptional coactivator OBF-1, which interacts with Oct-1 and Oct-2 and the octamer site DNA, has been shown to be critical for development of a normal immune response and the formation of germinal centers in secondary lymphoid organs. Here we have identified the RING finger protein Siah-1 as a protein interacting specifically with OBF-1. This interaction is mediated by the C-terminal part of Siah-1 and by residues in the N-terminus of OBF-1, partly distinct from the residues required for formation of a complex with the Oct POU domains and the DNA. Interaction between Siah-1 and OBF-1 leads to down-regulation of OBF-1 protein level but not mRNA, and to a corresponding reduction in octamer site-dependent transcription activation. Inhibition of the ubiquitin-proteasome pathway in B cells leads to elevated levels of OBF-1 protein. Furthermore, in immunized mice, OBF-1 protein amounts are dramatically increased in primary activated B cells, without concomitant increase in OBF-1 mRNA. These data suggest that Siah-1 is part of a novel regulatory loop controlling the level of OBF-1 protein in B cells.

Original languageEnglish (US)
Pages (from-to)4143-4152
Number of pages10
JournalEMBO Journal
Volume20
Issue number15
DOIs
StatePublished - Aug 1 2001
Externally publishedYes

Fingerprint

B-Lymphocytes
Cells
Proteins
Messenger RNA
Germinal Center
DNA
Proteasome Endopeptidase Complex
Ubiquitin
Transcriptional Activation
Transcription
Down-Regulation
Chemical activation
IgA receptor
Mouse Pou2af1 protein

Keywords

  • B cell transcription
  • OBF-1
  • RING finger proteins
  • Ubiquitin-proteasome pathway

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1. / Tiedt, R.; Bartholdy, Boris A.; Matthias, G.; Newell, J. W.; Matthias, P.

In: EMBO Journal, Vol. 20, No. 15, 01.08.2001, p. 4143-4152.

Research output: Contribution to journalArticle

Tiedt, R. ; Bartholdy, Boris A. ; Matthias, G. ; Newell, J. W. ; Matthias, P. / The RING finger protein Siah-1 regulates the level of the transcriptional coactivator OBF-1. In: EMBO Journal. 2001 ; Vol. 20, No. 15. pp. 4143-4152.
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