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Characterization of the novel interaction between muskelin and TBX20, a critical cardiogenic transcription factor.

Abstract：

:The genetic regulation necessary for the formation of a four-chambered heart is tightly regulated by transcription factors such as TBX20, a member of the T-box (TBX) transcription factor family. TBX20 is critical for proper cardiogenesis and is expressed in the heart throughout development. Missense mutations in TBX20 have been found in patients with congenital heart defects (CHD). Characterization of modifiers of TBX20 activity will help elucidate the genetic mechanisms of heart development and CHD. A yeast two-hybrid assay screening an embryonic mouse heart cDNA library with TBX20b as bait was used to identify potential modifiers of TBX20 activity and identified an interaction with muskelin (MKLN1), a primarily cytoplasmic protein with potential roles in signal transduction machinery scaffolding and nucleocytoplasmic protein shuttling. In cellular studies, MKLN1 directly binds to the T-box DNA-binding domain of only the TBX20b isoform by its kelch repeats domain. Immunostaining of mammalian cells transfected with tagged TBX20b and MKLN1 revealed colocalization primarily in the cytoplasm. Immunohistochemistry analysis of embryonic mouse hearts reveals coexpression in the developing endocardial valvular and myocardial interventricular cells. This novel interaction between TBX20b and MKLN1 may help elucidate new regulatory mechanisms within heart development.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Debenedittis P,Harmelink C,Chen Y,Wang Q,Jiao K

doi

10.1016/j.bbrc.2011.05.020

subject

Has Abstract

pub_date

2011-06-03 00:00:00

pages

338-43

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(11)00773-X

journal_volume

409

pub_type

杂志文章

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