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

Citation
Ha. Kester et al., Transforming growth factor-beta-stimulated clone-22 is a member of a family of leucine zipper proteins that can homo- and heterodimerize and has transcriptional repressor activity, J BIOL CHEM, 274(39), 1999, pp. 27439-27447
Citations number
38
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
39
Year of publication
1999
Pages
27439 - 27447
Database
ISI
SICI code
0021-9258(19990924)274:39<27439:TGFCIA>2.0.ZU;2-7
Abstract
TGF-beta-stimulated clone-22 (TSC-22) encodes a leucine zipper-containing p rotein that is highly conserved during evolution. Two homologues are known that share a similar leucine zipper domain and another conserved domain (de signated the TSC box). Only limited data are available on the function of T SC-22 and its homologues. TSC-22 is transcriptionally up-regulated by many different stimuli, including anti-cancer drugs and growth inhibitors, and r ecent 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 leuc ine zipper domain. Using a yeast two-hybrid screen, we identified a TSC-22 homologue (THG-1) as heterodimeric partner. Furthermore, we report the pres ence of two more mammalian family members with highly conserved leucine zip pers and TSC boxes. Interestingly, both TSC-22 and THG-1 have transcription al repressor activity when fused to a heterologous DNA-binding domain. The repressor activity of TSC-22 appears sensitive for promoter architecture, b ut not for the histone deacetylase inhibitor trichostatin A. Mutational ana lysis showed that this repressor activity resides in the non-conserved regi ons of the protein and is enhanced by the conserved dimerization domain. Ou r results suggest that TSC-22 belongs to a family of leucine zipper-contain ing transcription factors that can homodimerize and heterodimerize with oth er family members and that at least two TSC-22 family members may be repres sors of transcription.