NDLI: Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

Content Provider	PubMed Central
Author	Lin, Huixian Li, Zhe Chen, Chang Luo, Xiaobin Xiao, Jiening Dong, Deli Lu, Yanjie Yang, Baofeng Wang, Zhiguo
Editor	Dryer, Stuart E.
Copyright Year	2011
Abstract	The human ether-à-go-go-1 (h-eag1) K+ channel is expressed in a variety of cell lines derived from human malignant tumors and in clinical samples of several different cancers, but is otherwise absent in normal tissues. It was found to be necessary for cell cycle progression and tumorigenesis. Specific inhibition of h-eag1 expression leads to inhibition of tumor cell proliferation. We report here that h-eag1 expression is controlled by the p53−miR-34−E2F1 pathway through a negative feed-forward mechanism. We first established E2F1 as a transactivator of h-eag1 gene through characterizing its promoter region. We then revealed that miR-34, a known transcriptional target of p53, is an important negative regulator of h-eag1 through dual mechanisms by directly repressing h-eag1 at the post-transcriptional level and indirectly silencing h-eag1 at the transcriptional level via repressing E2F1. There is a strong inverse relationship between the expression levels of miR-34 and h-eag1 protein. H-eag1antisense antagonized the growth-stimulating effects and the upregulation of h-eag1 expression in SHSY5Y cells, induced by knockdown of miR-34, E2F1 overexpression, or inhibition of p53 activity. Therefore, p53 negatively regulates h-eag1 expression by a negative feed-forward mechanism through the p53−miR-34−E2F1 pathway. Inactivation of p53 activity, as is the case in many cancers, can thus cause oncogenic overexpression of h-eag1 by relieving the negative feed-forward regulation. These findings not only help us understand the molecular mechanisms for oncogenic overexpression of h-eag1 in tumorigenesis but also uncover the cell-cycle regulation through the p53−miR-34−E2F1−h-eag1 pathway. Moreover, these findings place h-eag1 in the p53−miR-34−E2F1−h-eag1 pathway with h-eag as a terminal effecter component and with miR-34 (and E2F1) as a linker between p53 and h-eag1. Our study therefore fills the gap between p53 pathway and its cellular function mediated by h-eag1.
Related Links	http://dx.doi.org/10.1371/journal.pone.0020362
Starting Page	20362
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	5
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-05-31
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Correction: Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K+ channel voltage sensor

Transfer of Voltage Independence from a Rat Olfactory Channel to the Drosophila Ether-à-go-go K+ Channel

Modulation of human ether-à-go-go-related K+ (HERG) channel inactivation by Cs+ and K+

Human Ether-à-go-go–related Gene K+ Channel Gating Probed with Extracellular Ca2+

Shaker and ether-à-go-go K+ channel subunits fail to coassemble in Xenopus oocytes.

A voltage-driven switch for ion-independent signaling by ether-à-go-go K+ channels

Cloning and functional expression of rat ether-à-go-go-like K+ channel genes

Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

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Correction: Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

Transcriptional and Post-Transcriptional Mechanisms for Oncogenic Overexpression of Ether À Go-Go K+ Channel

Optical detection of rate-determining ion-modulated conformational changes of the ether-à-go-go K+ channel voltage sensor

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