Transforming growth factor-β-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity

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Abstract

TGF-β-stimulated clone-22 (TSC-22) encodes a leucine zipper-containing protein that is highly conserved during evolution. Two homologues are known that share a similar leucine zipper domain and another conserved domain (designated the TSC box). Only limited data are available on the function of TSC-22 and its homologues. TSC-22 is transcriptionally up-regulated by many different stimuli, including anti-cancer drugs and growth inhibitors, and recent data suggest that TSC-22 may play a suppressive role in tumorigenesis. In this paper we show that TSC-22 forms homodimers via its conserved leucine zipper domain. Using a yeast two-hybrid screen, we identified a TSC-22 homologue (THG-1) as heterodimeric partner. Furthermore, we report the presence of two more mammalian family members with highly conserved leucine zippers and TSC boxes. Interestingly, both TSC-22 and THG-1 have transcriptional repressor activity when fused to a heterologous DNA-binding domain. The repressor activity of TSC-22 appears sensitive for promoter architecture, but not for the histone deacetylase inhibitor trichostatin A. Mutational analysis showed that this repressor activity resides in the non- conserved regions of the protein and is enhanced by the conserved dimerization domain. Our results suggest that TSC-22 belongs to a family of leucine zipper-containing transcription factors that can homodimerize and heterodimerize with other family members and that at least two TSC-22 family members may be repressors of transcription.

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Kester, H. A., Blanchetot, C., Den Hertog, J., Van Der Saag, P. T., & Van Der Burg, B. (1999). Transforming growth factor-β-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity. Journal of Biological Chemistry, 274(39), 27439–27447. https://doi.org/10.1074/jbc.274.39.27439

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