Proteasomal selection of multiprotein complexes recruited by LIM homeodomain transcription factors

Cenap Güngör, Naoko Taniguchi-Ishigaki, Hong Ma, Alexander Drung, Baris Tursun, Heather P. Ostendorff, Michael Bossenz, Catherina G. Becker, Thomas Becker, Ingolf Bach

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37 Scopus citations

Abstract

Complexes composed of multiple proteins regulate most cellular functions. However, our knowledge about the molecular mechanisms governing the assembly and dynamics of these complexes in cells remains limited. The in vivo activity of LIM homeodomain (LIM-HD) proteins, a class of transcription factors that regulates neuronal development, depends on the high-affinity association of their LIM domains with cofactor of LIM homeodomain proteins (LIM-HDs) (CLIM, also known as Ldb or NLI). CLIM cofactors recruit single-stranded DNA-binding protein 1 (SSDP1, also known as SSBP3), and this interaction is important for the activation of the LIM-HD/CLIM protein complex in vivo. Here, we identify a cascade of specific protein interactions that protect LIM-HD multiprotein complexes from proteasomal degradation. In this cascade, CLIM stabilizes LIM-HDs, and SSDP1 stabilizes CLIM. Furthermore, we show that stabilizing cofactors prevent binding of ubiquitin ligases to multiple protein interaction domains in LIM-HD recruited protein complexes. Together, our results indicate a combinatorial code that selects specific multiprotein complexes via proteasomal degradation in cells with broad implications for the assembly and specificity of multiprotein complexes.

Original languageEnglish (US)
Pages (from-to)15000-15005
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number38
DOIs
StatePublished - Sep 18 2007

All Science Journal Classification (ASJC) codes

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    Güngör, C., Taniguchi-Ishigaki, N., Ma, H., Drung, A., Tursun, B., Ostendorff, H. P., Bossenz, M., Becker, C. G., Becker, T., & Bach, I. (2007). Proteasomal selection of multiprotein complexes recruited by LIM homeodomain transcription factors. Proceedings of the National Academy of Sciences of the United States of America, 104(38), 15000-15005. https://doi.org/10.1073/pnas.0703738104