A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity.
Williams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activit...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2015-01-01
|
Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC4676684?pdf=render |
id |
doaj-452b490133a9419587d15b726ecb7b7f |
---|---|
record_format |
Article |
spelling |
doaj-452b490133a9419587d15b726ecb7b7f2020-11-25T00:23:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014475310.1371/journal.pone.0144753A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity.Kateřina CetkovskáHana ŠustováPavlína KosztyuStjepan UldrijanWilliams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activity in a significant proportion of human cancers, was identified in this study as a new binding partner for TFII-I and a negative regulator of TFII-I-mediated transcription. These findings suggest a new p53-independent mechanism by which increased Mdm2 levels found in human tumors could influence cancer cells. In addition to that, we present data indicating that TFII-I is an important cellular regulator of transcription from the immediate-early promoter of human cytomegalovirus, a promoter sequence frequently used in mammalian expression vectors, including vectors for gene therapy. Our observation that Mdm2 over-expression can decrease the ability of TFII-I to activate the CMV promoter might have implications for the efficiency of experimental gene therapy based on CMV promoter-derived vectors in cancers with Mdm2 gene amplification.http://europepmc.org/articles/PMC4676684?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kateřina Cetkovská Hana Šustová Pavlína Kosztyu Stjepan Uldrijan |
spellingShingle |
Kateřina Cetkovská Hana Šustová Pavlína Kosztyu Stjepan Uldrijan A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity. PLoS ONE |
author_facet |
Kateřina Cetkovská Hana Šustová Pavlína Kosztyu Stjepan Uldrijan |
author_sort |
Kateřina Cetkovská |
title |
A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity. |
title_short |
A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity. |
title_full |
A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity. |
title_fullStr |
A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity. |
title_full_unstemmed |
A Novel Interaction between TFII-I and Mdm2 with a Negative Effect on TFII-I Transcriptional Activity. |
title_sort |
novel interaction between tfii-i and mdm2 with a negative effect on tfii-i transcriptional activity. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
Williams-Beuren syndrome-associated transcription factor TFII-I plays a critical regulatory role in bone and neural tissue development and in immunity, in part by regulating cell proliferation in response to mitogens. Mdm2, a cellular oncogene responsible for the loss of p53 tumor suppressor activity in a significant proportion of human cancers, was identified in this study as a new binding partner for TFII-I and a negative regulator of TFII-I-mediated transcription. These findings suggest a new p53-independent mechanism by which increased Mdm2 levels found in human tumors could influence cancer cells. In addition to that, we present data indicating that TFII-I is an important cellular regulator of transcription from the immediate-early promoter of human cytomegalovirus, a promoter sequence frequently used in mammalian expression vectors, including vectors for gene therapy. Our observation that Mdm2 over-expression can decrease the ability of TFII-I to activate the CMV promoter might have implications for the efficiency of experimental gene therapy based on CMV promoter-derived vectors in cancers with Mdm2 gene amplification. |
url |
http://europepmc.org/articles/PMC4676684?pdf=render |
work_keys_str_mv |
AT katerinacetkovska anovelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity AT hanasustova anovelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity AT pavlinakosztyu anovelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity AT stjepanuldrijan anovelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity AT katerinacetkovska novelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity AT hanasustova novelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity AT pavlinakosztyu novelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity AT stjepanuldrijan novelinteractionbetweentfiiiandmdm2withanegativeeffectontfiiitranscriptionalactivity |
_version_ |
1725355860681555968 |