The complex regulation of HIC (Human I-mfa domain containing protein) expression.

Human I-mfa domain containing protein (HIC) differentially regulates transcription from viral promoters. HIC affects the Wnt pathway, the JNK/SAPK pathway and the activity of positive transcription elongation factor-b (P-TEFb). Studies exploring HIC function in mammalian cells used ectopically expre...

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Main Authors: Ella Reiss-Sklan, Alexander Levitzki, Tally Naveh-Many
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2009-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2701633?pdf=render
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author Ella Reiss-Sklan
Alexander Levitzki
Tally Naveh-Many
author_facet Ella Reiss-Sklan
Alexander Levitzki
Tally Naveh-Many
author_sort Ella Reiss-Sklan
collection DOAJ
description Human I-mfa domain containing protein (HIC) differentially regulates transcription from viral promoters. HIC affects the Wnt pathway, the JNK/SAPK pathway and the activity of positive transcription elongation factor-b (P-TEFb). Studies exploring HIC function in mammalian cells used ectopically expressed HIC due to undetected endogenous HIC protein. HIC mRNA contains exceptionally long 5' and 3' untranslated regions (UTRs) compared to the average length of mRNA UTRs. Here we show that HIC protein is subject to strict repression at multiple levels. The HIC mRNA UTRs reduce the expression of HIC or of a reporter protein: The HIC 3'-UTR decreases both HIC and reporter mRNA levels, whereas upstream open reading frames located in the 5'-UTR repress the translation of HIC or of the reporter protein. In addition, ectopically expressed HIC protein is degraded by the proteasome, with a half-life of approximately 1 h, suggesting that upon activation, HIC expression in cells may be transient. The strict regulation of HIC expression at the levels of mRNA stability, translation efficiency and protein stability suggests that expression of the HIC protein and its involvement in the various pathways is required only under specific cellular conditions.
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spelling doaj.art-32a692facb7a40318091218b6ada9fda2022-12-21T23:45:59ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0147e615210.1371/journal.pone.0006152The complex regulation of HIC (Human I-mfa domain containing protein) expression.Ella Reiss-SklanAlexander LevitzkiTally Naveh-ManyHuman I-mfa domain containing protein (HIC) differentially regulates transcription from viral promoters. HIC affects the Wnt pathway, the JNK/SAPK pathway and the activity of positive transcription elongation factor-b (P-TEFb). Studies exploring HIC function in mammalian cells used ectopically expressed HIC due to undetected endogenous HIC protein. HIC mRNA contains exceptionally long 5' and 3' untranslated regions (UTRs) compared to the average length of mRNA UTRs. Here we show that HIC protein is subject to strict repression at multiple levels. The HIC mRNA UTRs reduce the expression of HIC or of a reporter protein: The HIC 3'-UTR decreases both HIC and reporter mRNA levels, whereas upstream open reading frames located in the 5'-UTR repress the translation of HIC or of the reporter protein. In addition, ectopically expressed HIC protein is degraded by the proteasome, with a half-life of approximately 1 h, suggesting that upon activation, HIC expression in cells may be transient. The strict regulation of HIC expression at the levels of mRNA stability, translation efficiency and protein stability suggests that expression of the HIC protein and its involvement in the various pathways is required only under specific cellular conditions.http://europepmc.org/articles/PMC2701633?pdf=render
spellingShingle Ella Reiss-Sklan
Alexander Levitzki
Tally Naveh-Many
The complex regulation of HIC (Human I-mfa domain containing protein) expression.
PLoS ONE
title The complex regulation of HIC (Human I-mfa domain containing protein) expression.
title_full The complex regulation of HIC (Human I-mfa domain containing protein) expression.
title_fullStr The complex regulation of HIC (Human I-mfa domain containing protein) expression.
title_full_unstemmed The complex regulation of HIC (Human I-mfa domain containing protein) expression.
title_short The complex regulation of HIC (Human I-mfa domain containing protein) expression.
title_sort complex regulation of hic human i mfa domain containing protein expression
url http://europepmc.org/articles/PMC2701633?pdf=render
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