HIC1 attenuates Wnt signaling by recruitment TCF-4 and β-catenin to the nuclear bodies EMBO Journal...
-
Upload
maria-summers -
Category
Documents
-
view
221 -
download
2
Transcript of HIC1 attenuates Wnt signaling by recruitment TCF-4 and β-catenin to the nuclear bodies EMBO Journal...
HIC1 attenuates Wnt signaling by recruitment TCF-4 and β-catenin to the nuclear bodies
EMBO Journal (2006)
Wnt signaling in the nucleus
Wnt Off
Wnt On
Wnt Off
(negative feedback)
(Xi He et al, Development, 2006)Groucho
HDAC
Wnt signaling in the nucleus
- In absence of Wnt,
◦ TCF/LEF-1- Bind constitutively to Wnt enhancers
- In presence of Wnt,
it can interact with corepressor, Groucho, HDAC, CBP
it can interact with coactivator, β-catenin, Pygo, Bcl9,
Chromatin remodeling complexes.
◦ CtBP- Transcriptional corepressor and APC-interacting protein
- Binding of CtBP is correlated with the loss of histone modification
(Karl Willert, Genes & Dev, 2006)
Introduction to HIC1 nuclear protein
◦ HIC1 (Hypermethylated in cancer 1)
- First identified as a tumor suppressor gene frequently epigenetically silenced or deleted in different type of solid tumors
(Herman JD et al, N Eng J Med, 2003)
- Hic +/- mice develop malignant tumor and densely methylated in wild type allele of Hic1 promoter
- CtBP associating protein and redirects CtBP to a specific set of nuclear dot-like structure called HIC1 bodies
(Chen et al, Nat Genet, 2003)
(Deltour et al, MCB, 2002)
What is the nuclear body ?
- The nuclear body is a discrete nuclear structure
- Cells typically contain 10–30 nuclear bodies per nucleus
- Each nuclear body has a unique function
(P. pandolfi et al, Nat cell biol, 2000)
HIC1 sequesters TCF-4 into nuclear bodiesBTB/POZ : protein-protein interaction
CtBP : CtBP binding domain (GLDLSKK)
HIC1 inhibits TCF/ β-catenin driven transcription
293 T cell Dimerizer regulated gene expression
(Roy pollock et al, Curr opinion, 2002)
Physiological meaning of HIC1
Regulating maximum limit of gene expression?
CtBP interacts with many of HATs
HDAC activity?