-
Something wrong with this record ?
Downregulation of p68 RNA helicase (DDX5) activates a survival pathway involving mTOR and MDM2 signals
M. Kokolo, M. Bach-Elias
Language English Country Czech Republic
Document type Journal Article
NLK
Free Medical Journals
from 2000
Freely Accessible Science Journals
from 2000
ProQuest Central
from 2005-01-01
Health & Medicine (ProQuest)
from 2005-01-01
ROAD: Directory of Open Access Scholarly Resources
from 2000
- MeSH
- Cell Cycle genetics physiology MeSH
- DEAD-box RNA Helicases genetics metabolism MeSH
- Phosphorylation genetics physiology MeSH
- HeLa Cells MeSH
- Humans MeSH
- Tumor Suppressor Protein p53 genetics metabolism MeSH
- Cell Proliferation physiology MeSH
- Proto-Oncogene Proteins c-mdm2 genetics metabolism MeSH
- RNA Interference MeSH
- TOR Serine-Threonine Kinases genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
The DEAD box p68 RNA helicase (DDX5) is required to manipulate RNA structures implicated in mRNA/rRNA processing and transcript export, and acts as a co-activator for a range of transcription factors. Previous research has indicated that p68 RNA helicase may also be important in tumour development. Wild-type HeLa and stable HeLa (clone 13) cell cultures containing RNAi-mediated depletion of p68 RNA helicase induced by doxycycline (DOX) were used to study how the p68 RNA helicase affects the mTOR cell signalling pathway. Relevant results were repeated using transient transfection with pSuper/pSuper-p68 RNA helicase, containing RNAi-mediated depletion of p68 RNA helicase, to avoid DOX interference. Here we provide strong evidence for the participation of p68 RNA helicase in mTOR regulation. In detail, depletion of this helicase decreases cell growth and activates the mTOR/MDM2 cell survival mechanism, which ultimately leads to inhibition of the pro-apoptotic activity. p68 RNA helicase downregulation strongly stimulates 4E-BP1 phosphorylation, thereby provoking activation of cap-dependent translation. In contrast, the IRES-dependent translation of c-myc is reduced when p68 RNA helicase is depleted, thus indicating that at least this specific translation requires p68 RNA helicase activity to manipulate the complex 5' end of this mRNA. Interestingly, p68 RNA helicase depletion decreases cell growth while activating the mTOR/MDM2 cell survival mechanism. As MDM2 is a known negative regulator of p53, we infer that the activation of the cell survival mechanism may result in inhibition of the pro-apoptotic factor p53. Finally, p68 RNA helicase depletion activates capdependent translation and inhibits c-MYC IRES-mediated translation.
- 000
- 00000naa a2200000 a 4500
- 001
- bmc18020892
- 003
- CZ-PrNML
- 005
- 20180723083947.0
- 007
- ta
- 008
- 180608s2017 xr d f 000 0|eng||
- 009
- AR
- 035 __
- $a (PubMed)28557706
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xr
- 100 1_
- $a Kokolo, M $u Institute of Biomedical Research of Barcelona - Spanish National Research Council (CSIC), Barcelona, Spain
- 245 10
- $a Downregulation of p68 RNA helicase (DDX5) activates a survival pathway involving mTOR and MDM2 signals / $c M. Kokolo, M. Bach-Elias
- 520 9_
- $a The DEAD box p68 RNA helicase (DDX5) is required to manipulate RNA structures implicated in mRNA/rRNA processing and transcript export, and acts as a co-activator for a range of transcription factors. Previous research has indicated that p68 RNA helicase may also be important in tumour development. Wild-type HeLa and stable HeLa (clone 13) cell cultures containing RNAi-mediated depletion of p68 RNA helicase induced by doxycycline (DOX) were used to study how the p68 RNA helicase affects the mTOR cell signalling pathway. Relevant results were repeated using transient transfection with pSuper/pSuper-p68 RNA helicase, containing RNAi-mediated depletion of p68 RNA helicase, to avoid DOX interference. Here we provide strong evidence for the participation of p68 RNA helicase in mTOR regulation. In detail, depletion of this helicase decreases cell growth and activates the mTOR/MDM2 cell survival mechanism, which ultimately leads to inhibition of the pro-apoptotic activity. p68 RNA helicase downregulation strongly stimulates 4E-BP1 phosphorylation, thereby provoking activation of cap-dependent translation. In contrast, the IRES-dependent translation of c-myc is reduced when p68 RNA helicase is depleted, thus indicating that at least this specific translation requires p68 RNA helicase activity to manipulate the complex 5' end of this mRNA. Interestingly, p68 RNA helicase depletion decreases cell growth while activating the mTOR/MDM2 cell survival mechanism. As MDM2 is a known negative regulator of p53, we infer that the activation of the cell survival mechanism may result in inhibition of the pro-apoptotic factor p53. Finally, p68 RNA helicase depletion activates capdependent translation and inhibits c-MYC IRES-mediated translation.
- 650 _2
- $a buněčný cyklus $x genetika $x fyziologie $7 D002453
- 650 _2
- $a proliferace buněk $x fyziologie $7 D049109
- 650 _2
- $a DEAD-box RNA-helikasy $x genetika $x metabolismus $7 D053487
- 650 _2
- $a HeLa buňky $7 D006367
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a fosforylace $x genetika $x fyziologie $7 D010766
- 650 _2
- $a protoonkogenní proteiny c-mdm2 $x genetika $x metabolismus $7 D051736
- 650 _2
- $a RNA interference $7 D034622
- 650 _2
- $a TOR serin-threoninkinasy $x genetika $x metabolismus $7 D058570
- 650 _2
- $a nádorový supresorový protein p53 $x genetika $x metabolismus $7 D016159
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Bach-Elias, M $u Institute of Biomedical Research of Barcelona - Spanish National Research Council (CSIC), Barcelona, Spain
- 773 0_
- $w MED00011004 $t Folia biologica $x 0015-5500 $g Roč. 63, č. 2 (2017), s. 52-59
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/28557706 $y Pubmed
- 856 41
- $u https://fb.cuni.cz/file/5838/fb2017a0009.pdf $y plný text volně přístupný
- 910 __
- $a ABA008 $b A 970 $c 89 $y 4 $z 0
- 990 __
- $a 20180608 $b ABA008
- 991 __
- $a 20180723084250 $b ABA008
- 999 __
- $a ok $b bmc $g 1320406 $s 1017754
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 63 $c 2 $d 52-59 $i 0015-5500 $m Folia biologica (Praha) $n Folia biol. (Praha) $x MED00011004
- LZP __
- $b NLK118 $a Pubmed-20180608