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  A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1

Lindner, J. M., Wong, C. S. F., Möller, A., & Nielsen, P. J. (2013). A C-Terminal Acidic Domain Regulates Degradation of the Transcriptional Coactivator Bob1. Molecular and Celllular Biology, 33, 4628-4640.

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 Creators:
Lindner, John M.1, Author
Wong, Christina S. F., Author
Möller, Andreas, Author
Nielsen, Peter J.2, Author              
Affiliations:
1Max Planck Society, ou_persistent13              
2Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243645              

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 Abstract: Bob1 (Obf-1 or OCA-B) is a 34-kDa transcriptional coactivator encoded by the Pou2af1 gene that is essential for normal B-cell development and immune responses in mice. During lymphocyte activation, Bob1 protein levels dramatically increase independently of mRNA levels, suggesting that the stability of Bob1 is regulated. We used a fluorescent protein-based reporter system to analyze protein stability in response to genetic and physiological perturbations and show that, while Bob1 degradation is proteasome mediated, it does not require ubiquitination of Bob1. Furthermore, degradation of Bob1 in B cells appears to be largely independent of the E3 ubiquitin ligase Siah. We propose a novel mechanism of Bob1 turnover in B cells, whereby an acidic region in the C terminus of Bob1 regulates the activity of degron signals elsewhere in the protein. Changes that make the C terminus more acidic, including tyrosine phosphorylation-mimetic mutations, stabilize the instable murine Bob1 protein, indicating that B cells may regulate Bob1 stability and activity via signaling pathways. Finally, we show that expressing a stable Bob1 mutant in B cells suppresses cell proliferation and induces changes in surface marker expression commonly seen during B-cell differentiation.

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Language(s): eng - English
 Dates: 2013
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: eDoc: 676035
 Degree: -

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Title: Molecular and Celllular Biology
  Alternative Title : MCB
Source Genre: Journal
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Pages: - Volume / Issue: 33 Sequence Number: - Start / End Page: 4628 - 4640 Identifier: -