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PMID: 9418910 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

LIM protein KyoT2 negatively regulates transcription by association with the RBP-J DNA-binding protein.

Molecular and cellular biology ·Vol. 18 ·No. 1 ·1998-01-00 ·Pages 644-54

Taniguchi Y, Furukawa T, Tun T, Han H, Honjo T

Abstract

The RBP-J/Su(H) DNA-binding protein plays a key role in transcriptional regulation by targeting Epstein-Barr virus nuclear antigen 2 (EBNA2) and the intracellular portions of Notch receptors to specific promoters. Using the yeast two-hybrid system, we isolated a LIM-only protein, KyoT, which physically interacts with RBP-J. Differential splicing gave rise to two transcripts of the KyoT gene, KyoT1 and KyoT2, that encoded proteins with four and two LIM domains, respectively. With differential splicing resulting in deletion of an exon, KyoT2 lacked two LIM domains from the C terminus and had a frameshift in the last exon, creating the RBP-J-binding region in the C terminus. KyoT1 had a negligible level of interaction with RBP-J. Strong expression of KyoT mRNAs was detected in skeletal muscle and lung, with a predominance of KyoT1 mRNA. When expressed in F9 embryonal carcinoma cells, KyoT1 and KyoT2 were localized in the cytoplasm and the nucleus, respectively. The binding site of KyoT2 on RBP-J overlaps those of EBNA2 and Notchl but is distinct from that of Hairless, the negative regulator of RBP-J-mediated transcription in Drosophila. KyoT2 but not KyoT1 repressed the RBP-J-mediated transcriptional activation by EBNA2 and Notch1 by competing with them for binding to RBP-J and by dislocating RBP-J from DNA. KyoT2 is a novel negative regulatory molecule for RBP-J-mediated transcription in mammalian systems.

MeSH Terms
Amino Acid Sequence Animals Base Sequence COS Cells DNA-Binding Proteins/genetics Homeodomain Proteins/genetics Molecular Sequence Data Transcription Factors/genetics Transcription, Genetic
Chemicals
DNA-Binding Proteins Homeodomain Proteins Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Taniguchi Y
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
Furukawa T
Tun T
Han H
Honjo T
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55 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.18.1.644
Published
1998-01-00
Pages
644-54
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC121531
Subset
IM
Databases
GENBANK
U41739
External Links
PubMed source DOI: 10.1128/MCB.18.1.644 PMC Full Text View journal details
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