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
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
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.