- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Theses and Dissertations /
- Overexpression of TDP-43 inhibits NF-κB activity by...
Open Collections
UBC Theses and Dissertations
UBC Theses and Dissertations
Overexpression of TDP-43 inhibits NF-κB activity by blocking p65 nuclear translocation Zhu, Jingyan
Abstract
TDP-43 (TAR DNA binding protein 43) is a heterogeneous nuclear ribonucleoprotein (hnRNP) that has been found to be mainly responsible for neurodegenerative diseases recently. Its involvement in nuclear factor-kappaB pathways has been reported in neuron and microglial cells that are linked to amyotrophic lateral sclerosis (ALS). Nuclear factor-kappaB (NF-κB) is a family that consists of five members that exist and function as dimers. NF-κB pathway targets more than hundreds of genes that are involved in inflammation, immunity and cancer. It also has functions in the nervous system. p50/p65 (p50/RelA) heterodimers, as the major Rel complex in the NF-κB family, are induced by diverse external physiological stimuli and modulate transcriptional activity in almost all cell types. Both p65 and TDP-43 translocation are through the classic nuclear transportation system. In this study, we report that TDP-43 overexpression could block TNF-α induced p65 nuclear translocation dose dependently that further inhibits p65 transactivation activity. Furthermore, the inhibition by TDP-43 is not through preventing IκB degradation but probably by competing the nuclear transporter-importin α3 (KPNA4) and this competition is dependent on the presence of NLS in TDP-43. Silencing TDP-43 by a specific siRNA also increased p65 nuclear localization upon TNF-α stimulation, suggesting that endogenous TDP-43 may be a default suppressor of NF-κB pathway. The above results indicate that TDP-43 may play an important role in regulating the levels of NF-κB activity by control the nuclear translocation of p65.
Item Metadata
Title |
Overexpression of TDP-43 inhibits NF-κB activity by blocking p65 nuclear translocation
|
Creator | |
Publisher |
University of British Columbia
|
Date Issued |
2013
|
Description |
TDP-43 (TAR DNA binding protein 43) is a heterogeneous nuclear ribonucleoprotein
(hnRNP) that has been found to be mainly responsible for neurodegenerative diseases
recently. Its involvement in nuclear factor-kappaB pathways has been reported in neuron and
microglial cells that are linked to amyotrophic lateral sclerosis (ALS). Nuclear factor-kappaB
(NF-κB) is a family that consists of five members that exist and function as dimers. NF-κB
pathway targets more than hundreds of genes that are involved in inflammation, immunity
and cancer. It also has functions in the nervous system. p50/p65 (p50/RelA) heterodimers, as
the major Rel complex in the NF-κB family, are induced by diverse external physiological
stimuli and modulate transcriptional activity in almost all cell types. Both p65 and TDP-43
translocation are through the classic nuclear transportation system. In this study, we report
that TDP-43 overexpression could block TNF-α induced p65 nuclear translocation dose
dependently that further inhibits p65 transactivation activity. Furthermore, the inhibition by
TDP-43 is not through preventing IκB degradation but probably by competing the nuclear
transporter-importin α3 (KPNA4) and this competition is dependent on the presence of NLS
in TDP-43. Silencing TDP-43 by a specific siRNA also increased p65 nuclear localization
upon TNF-α stimulation, suggesting that endogenous TDP-43 may be a default suppressor of
NF-κB pathway. The above results indicate that TDP-43 may play an important role in
regulating the levels of NF-κB activity by control the nuclear translocation of p65.
|
Genre | |
Type | |
Language |
eng
|
Date Available |
2013-04-18
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
|
DOI |
10.14288/1.0073733
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Graduation Date |
2013-05
|
Campus | |
Scholarly Level |
Graduate
|
Rights URI | |
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International