Repression of Smad3 activity by histone demethylase SMCX/JARID1C.

Abstract:

:SMCX/JARID1C was recently shown to be a histone H3 lysine 4 (H3K4) demethylase. Here, we have identified an SMCX isoform that predominantly resides in the cytoplasm, but still efficiently demethylates trimethylated H3K4. SMCX requires several functional domains for its demethylase activity and is also capable of forming homomers through amino acids 204-493. Further, SMCX physically interacts with Smad3, a mediator of transforming growth factor-beta (TGF-beta), and overexpression of SMCX inhibits the ability of Smad3 to activate transcription. Thus, SMCX is a novel Smad3 corepressor that may antagonize the tumor suppressing activity of the TGF-beta/Smad3 signaling pathway and thereby contribute to tumorigenesis. Indeed, SMCX is overexpressed in prostate tumors and seminomas, suggesting that SMCX might be a novel oncogene.

authors

Kim TD,Shin S,Janknecht R

doi

10.1016/j.bbrc.2007.12.013

subject

Has Abstract

pub_date

2008-02-08 00:00:00

pages

563-7

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(07)02619-8

journal_volume

366

pub_type

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