The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F19%3A00078139" target="_blank" >RIV/00209805:_____/19:00078139 - isvavai.cz</a>
Result on the web
<a href="https://reader.elsevier.com/reader/sd/pii/S0898656819300750?token=C0C802C9CDCBF8472C1FDD4ED1FEADFBBD0B5F644FCE67594191885825C4D59741904676EECA326A3BEA989E5CDD5407" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S0898656819300750?token=C0C802C9CDCBF8472C1FDD4ED1FEADFBBD0B5F644FCE67594191885825C4D59741904676EECA326A3BEA989E5CDD5407</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.cellsig.2019.03.024" target="_blank" >10.1016/j.cellsig.2019.03.024</a>
Alternative languages
Result language
angličtina
Original language name
The effects of IFITM1 and IFITM3 gene deletion on IFNγ stimulated protein synthesis
Original language description
Interferon-induced transmembrane proteins IFITM1 and IFITM3 (IFITM1/3) play a role in both RNA viral restriction and in human cancer progression. Using immunohistochemical staining of FFPE tissue, we identified subgroups of cervical cancer patients where IFITM1/3 protein expression is inversely related to metastasis. Guide RNA-CAS9 methods were used to develop an isogenic IFITM1/IFITM3 double null cervical cancer model in order to define dominant pathways triggered by presence or absence of IFITM1/3 signalling. A pulse SILAC methodology identified IRF1, HLA-B, and ISG15 as the most dominating IFNγ inducible proteins whose synthesis was attenuated in the IFITM1/IFITM3 double-null cells. Conversely, SWATH-IP mass spectrometry of ectopically expressed SBP-tagged IFITM1 identified ISG15 and HLA-B as dominant co-associated proteins. ISG15ylation was attenuated in IFNγ treated IFITM1/IFITM3 double-null cells. Proximity ligation assays indicated that HLA-B can interact with IFITM1/3 proteins in parental SiHa cells. Cell surface expression of HLA-B was attenuated in IFNγ treated IFITM1/IFITM3 double-null cells. SWATH-MS proteomic screens in cells treated with IFITM1-targeted siRNA cells resulted in the attenuation of an interferon regulated protein subpopulation including MHC Class I molecules as well as IFITM3, STAT1, B2M, and ISG15. These data have implications for the function of IFITM1/ 3 in mediating IFNγ stimulated protein synthesis including ISG15ylation and MHC Class I production in cancer cells. The data together suggest that pro-metastatic growth associated with IFITM1/3 negative cervical cancers relates to attenuated expression of MHC Class I molecules that would support tumor immune escape.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cellular signalling
ISSN
0898-6568
e-ISSN
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Volume of the periodical
60
Issue of the periodical within the volume
August 2019
Country of publishing house
US - UNITED STATES
Number of pages
18
Pages from-to
39-56
UT code for WoS article
000471356700004
EID of the result in the Scopus database
2-s2.0-85064179749