PMID- 10488076 OWN - NLM STAT- MEDLINE DCOM- 19991104 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 274 IP - 39 DP - 1999 Sep 24 TI - 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. PG - 27439-47 AB - TGF-beta-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. FAU - Kester, H A AU - Kester HA AD - Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands. FAU - Blanchetot, C AU - Blanchetot C FAU - den Hertog, J AU - den Hertog J FAU - van der Saag, P T AU - van der Saag PT FAU - van der Burg, B AU - van der Burg B LA - eng SI - GENBANK/AJ133115 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Recombinant Fusion Proteins) RN - 0 (Repressor Proteins) RN - 0 (TSC22D1 protein, human) SB - IM MH - Amino Acid Sequence MH - Animals MH - Base Sequence MH - COS Cells MH - Conserved Sequence MH - Dimerization MH - Evolution, Molecular MH - *Gene Expression Regulation MH - Humans MH - *Leucine Zippers MH - Molecular Sequence Data MH - Recombinant Fusion Proteins/metabolism MH - Repressor Proteins/chemistry/*genetics/*metabolism MH - Sequence Alignment MH - Sequence Homology, Amino Acid MH - *Transcription, Genetic MH - Transfection EDAT- 1999/09/17 00:00 MHDA- 1999/09/17 00:01 CRDT- 1999/09/17 00:00 PHST- 1999/09/17 00:00 [pubmed] PHST- 1999/09/17 00:01 [medline] PHST- 1999/09/17 00:00 [entrez] AID - 10.1074/jbc.274.39.27439 [doi] AID - S0021-9258(19)52139-1 [pii] PST - ppublish SO - J Biol Chem. 1999 Sep 24;274(39):27439-47. doi: 10.1074/jbc.274.39.27439.