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...
Main Authors: | , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2009-01-01
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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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institution | Directory Open Access Journal |
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language | English |
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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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