Groucho suppresses Pax2 transactivation by inhibition of JNK-mediated phosphorylation The EMBO...
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Transcript of Groucho suppresses Pax2 transactivation by inhibition of JNK-mediated phosphorylation The EMBO...
Groucho suppresses Pax2 transactivation byinhibition of JNK-mediated phosphorylation
The EMBO Journal Vol. 22 No. 20 pp. 5522-5529, 2003
-human Groucho family: TLE-1/2/3/4 (transducin-like enhancer of split) hAES(amino-termianl enhancer of split)
-mouse Groucho family: Grg-1/2/3/4 & Grg-5
Q domain: glutamine rich
GP domain: glycine/proline rich
CcN domain
SP domain:serine/proline rich
Four WD40 repeats domain
tetramerization(leucine zipper-like structure)binding to n-terminal of H3Interaction with HDAC
Putative casein kinase II/cdc2 phosphorylation sitesnuclear localization signal
protein interaction
Pax: paired box gene-pax 1~9, DNA binding transcription factor-activation and repression of downstream target genes-regulators of organogenesis & key factors in maintaining pluripotency of
stem cell populations during development-Mutations of the Pax: profound developmental defects in organisms as
diverse as flies, mice and humans.
PD domain: bipartite paired domain N- & C-terminal subdomains three α-helices third helix of each subdomain (red) contact with the major groove of DNA
OP motif: octapeptide motif HD domain: homeodomain helix–turn–helix structure.
TD domain: C-term transactivation domain
Pax2/5/8-the Pax2/5/8 proteins contain a conserved octapeptide with homology to
the engrailed-type repressor sequence.
OP domain
Engrailed homology region of the homeodomain transcription factors EN2 and Goosecoid(GSC)
-pax 2/5/8 contains partial homeodomain(HD1) that consistutes an interation surface for both the retinoblastoma(Rb) gene product and the TATA-binding protein (Eberhard and busslinger,1999)
- The ability of Pax2 to activate transcription is enhanced by phosphorylation of its activation domain by the JNK (Cai et al., 2002)
Pax2-JNK-groucho
- Pax5 transactivation activity can also be negatively regulated through interactions with the Groucho/TLE family of co-repressors (Eberhard et al.,2000)
-In mouse and man, the Pax2 gene is essential for the developmentof the kidneys, optic cup, and inner ear.
-SFRP2 gene is a target of the Pax2 transcription factor (J Biol Chem.2003 )
TSA(trichostatin A): HDAC inhibitor
Fig. 2. Grg4 inhibits the JNK enhanced transactivation potential of Pax2.
Gal4 DNA binding element luciGal 4 DNA binding domain
Activation domain Elk or c-Jun
Fig. 3. Grg4 inhibits phosphorylation of Pax2 in a DNA-dependent manner
In vivo phospho-labeling of 293 cells