---
_id: '1678'
abstract:
- lang: eng
text: High-throughput live-cell screens are intricate elements of systems biology
studies and drug discovery pipelines. Here, we demonstrate an optogenetics-assisted
method that avoids the need for chemical activators and reporters, reduces the
number of operational steps and increases information content in a cell-based
small-molecule screen against human protein kinases, including an orphan receptor
tyrosine kinase. This blueprint for all-optical screening can be adapted to many
drug targets and cellular processes.
acknowledgement: 'This work was supported by grants from the European Union Seventh
Framework Programme (CIG-303564 to H.J. and ERC-StG-311166 to S.M.B.N.), the Human
Frontier Science Program (RGY0084_2012 to H.J.) and the Herzfelder Foundation (to
M.G.). A.I.-P. was supported by a Ramon Areces fellowship, and E.R. by the graduate
program MolecularDrugTargets (Austrian Science Fund (FWF): W 1232) and a FemTech
fellowship (3580812 Austrian Research Promotion Agency).'
author:
- first_name: Álvaro
full_name: Inglés Prieto, Álvaro
id: 2A9DB292-F248-11E8-B48F-1D18A9856A87
last_name: Inglés Prieto
orcid: 0000-0002-5409-8571
- first_name: Eva
full_name: Gschaider-Reichhart, Eva
id: 3FEE232A-F248-11E8-B48F-1D18A9856A87
last_name: Gschaider-Reichhart
orcid: 0000-0002-7218-7738
- first_name: Markus
full_name: Muellner, Markus
last_name: Muellner
- first_name: Matthias
full_name: Nowak, Matthias
id: 30845DAA-F248-11E8-B48F-1D18A9856A87
last_name: Nowak
- first_name: Sebastian
full_name: Nijman, Sebastian
last_name: Nijman
- first_name: Michael
full_name: Grusch, Michael
last_name: Grusch
- first_name: Harald L
full_name: Janovjak, Harald L
id: 33BA6C30-F248-11E8-B48F-1D18A9856A87
last_name: Janovjak
orcid: 0000-0002-8023-9315
citation:
ama: Inglés Prieto Á, Gschaider-Reichhart E, Muellner M, et al. Light-assisted small-molecule
screening against protein kinases. Nature Chemical Biology. 2015;11(12):952-954.
doi:10.1038/nchembio.1933
apa: Inglés Prieto, Á., Gschaider-Reichhart, E., Muellner, M., Nowak, M., Nijman,
S., Grusch, M., & Janovjak, H. L. (2015). Light-assisted small-molecule screening
against protein kinases. Nature Chemical Biology. Nature Publishing Group.
https://doi.org/10.1038/nchembio.1933
chicago: Inglés Prieto, Álvaro, Eva Gschaider-Reichhart, Markus Muellner, Matthias
Nowak, Sebastian Nijman, Michael Grusch, and Harald L Janovjak. “Light-Assisted
Small-Molecule Screening against Protein Kinases.” Nature Chemical Biology.
Nature Publishing Group, 2015. https://doi.org/10.1038/nchembio.1933.
ieee: Á. Inglés Prieto et al., “Light-assisted small-molecule screening against
protein kinases,” Nature Chemical Biology, vol. 11, no. 12. Nature Publishing
Group, pp. 952–954, 2015.
ista: Inglés Prieto Á, Gschaider-Reichhart E, Muellner M, Nowak M, Nijman S, Grusch
M, Janovjak HL. 2015. Light-assisted small-molecule screening against protein
kinases. Nature Chemical Biology. 11(12), 952–954.
mla: Inglés Prieto, Álvaro, et al. “Light-Assisted Small-Molecule Screening against
Protein Kinases.” Nature Chemical Biology, vol. 11, no. 12, Nature Publishing
Group, 2015, pp. 952–54, doi:10.1038/nchembio.1933.
short: Á. Inglés Prieto, E. Gschaider-Reichhart, M. Muellner, M. Nowak, S. Nijman,
M. Grusch, H.L. Janovjak, Nature Chemical Biology 11 (2015) 952–954.
date_created: 2018-12-11T11:53:25Z
date_published: 2015-10-12T00:00:00Z
date_updated: 2023-09-07T12:49:09Z
day: '12'
ddc:
- '571'
department:
- _id: HaJa
- _id: LifeSc
doi: 10.1038/nchembio.1933
ec_funded: 1
file:
- access_level: open_access
checksum: e9fb251dfcb7cd209b83f17867e61321
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:10:51Z
date_updated: 2020-07-14T12:45:12Z
file_id: '4842'
file_name: IST-2017-837-v1+1_ingles-prieto.pdf
file_size: 1308364
relation: main_file
file_date_updated: 2020-07-14T12:45:12Z
has_accepted_license: '1'
intvolume: ' 11'
issue: '12'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Submitted Version
page: 952 - 954
project:
- _id: 25548C20-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '303564'
name: Microbial Ion Channels for Synthetic Neurobiology
- _id: 255BFFFA-B435-11E9-9278-68D0E5697425
grant_number: RGY0084/2012
name: In situ real-time imaging of neurotransmitter signaling using designer optical
sensors (HFSP Young Investigator)
- _id: 255A6082-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
publication: Nature Chemical Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '5471'
pubrep_id: '837'
quality_controlled: '1'
related_material:
record:
- id: '418'
relation: dissertation_contains
status: public
scopus_import: 1
status: public
title: Light-assisted small-molecule screening against protein kinases
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2015'
...
---
_id: '1848'
abstract:
- lang: eng
text: The ability to escape apoptosis is a hallmark of cancer-initiating cells and
a key factor of resistance to oncolytic therapy. Here, we identify FAM96A as a
ubiquitous, evolutionarily conserved apoptosome-activating protein and investigate
its potential pro-apoptotic tumor suppressor function in gastrointestinal stromal
tumors (GISTs). Interaction between FAM96A and apoptotic peptidase activating
factor 1 (APAF1) was identified in yeast two-hybrid screen and further studied
by deletion mutants, glutathione-S-transferase pull-down, co-immunoprecipitation
and immunofluorescence. Effects of FAM96A overexpression and knock-down on apoptosis
sensitivity were examined in cancer cells and zebrafish embryos. Expression of
FAM96A in GISTs and histogenetically related cells including interstitial cells
of Cajal (ICCs), “fibroblast-like cells” (FLCs) and ICC stem cells (ICC-SCs) was
investigated by Northern blotting, reverse transcription—polymerase chain reaction,
immunohistochemistry and Western immunoblotting. Tumorigenicity of GIST cells
and transformed murine ICC-SCs stably transduced to re-express FAM96A was studied
by xeno- and allografting into immunocompromised mice. FAM96A was found to bind
APAF1 and to enhance the induction of mitochondrial apoptosis. FAM96A protein
or mRNA was dramatically reduced or lost in 106 of 108 GIST samples representing
three independent patient cohorts. Whereas ICCs, ICC-SCs and FLCs, the presumed
normal counterparts of GIST, were found to robustly express FAM96A protein and
mRNA, FAM96A expression was much reduced in tumorigenic ICC-SCs. Re-expression
of FAM96A in GIST cells and transformed ICC-SCs increased apoptosis sensitivity
and diminished tumorigenicity. Our data suggest FAM96A is a novel pro-apoptotic
tumor suppressor that is lost during GIST tumorigenesis.
article_processing_charge: No
article_type: original
author:
- first_name: Bettina
full_name: Schwamb, Bettina
last_name: Schwamb
- first_name: Robert
full_name: Pick, Robert
last_name: Pick
- first_name: Sara
full_name: Fernández, Sara
last_name: Fernández
- first_name: Kirsten
full_name: Völp, Kirsten
last_name: Völp
- first_name: Jan
full_name: Heering, Jan
last_name: Heering
- first_name: Volker
full_name: Dötsch, Volker
last_name: Dötsch
- first_name: Susanne
full_name: Bösser, Susanne
last_name: Bösser
- first_name: Jennifer
full_name: Jung, Jennifer
last_name: Jung
- first_name: Rasa
full_name: Beinoravičiute Kellner, Rasa
last_name: Beinoravičiute Kellner
- first_name: Josephine
full_name: Wesely, Josephine
last_name: Wesely
- first_name: Inka
full_name: Zörnig, Inka
last_name: Zörnig
- first_name: Matthias
full_name: Hammerschmidt, Matthias
last_name: Hammerschmidt
- first_name: Matthias
full_name: Nowak, Matthias
id: 30845DAA-F248-11E8-B48F-1D18A9856A87
last_name: Nowak
- first_name: Roland
full_name: Penzel, Roland
last_name: Penzel
- first_name: Kurt
full_name: Zatloukal, Kurt
last_name: Zatloukal
- first_name: Stefan
full_name: Joos, Stefan
last_name: Joos
- first_name: Ralf
full_name: Rieker, Ralf
last_name: Rieker
- first_name: Abbas
full_name: Agaimy, Abbas
last_name: Agaimy
- first_name: Stephan
full_name: Söder, Stephan
last_name: Söder
- first_name: Kmarie
full_name: Reid Lombardo, Kmarie
last_name: Reid Lombardo
- first_name: Michael
full_name: Kendrick, Michael
last_name: Kendrick
- first_name: Michael
full_name: Bardsley, Michael
last_name: Bardsley
- first_name: Yujiro
full_name: Hayashi, Yujiro
last_name: Hayashi
- first_name: David
full_name: Asuzu, David
last_name: Asuzu
- first_name: Sabriya
full_name: Syed, Sabriya
last_name: Syed
- first_name: Tamás
full_name: Ördög, Tamás
last_name: Ördög
- first_name: Martin
full_name: Zörnig, Martin
last_name: Zörnig
citation:
ama: Schwamb B, Pick R, Fernández S, et al. FAM96A is a novel pro-apoptotic tumor
suppressor in gastrointestinal stromal tumors. International Journal of Cancer.
2015;137(6):1318-1329. doi:10.1002/ijc.29498
apa: Schwamb, B., Pick, R., Fernández, S., Völp, K., Heering, J., Dötsch, V., …
Zörnig, M. (2015). FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal
stromal tumors. International Journal of Cancer. Wiley. https://doi.org/10.1002/ijc.29498
chicago: Schwamb, Bettina, Robert Pick, Sara Fernández, Kirsten Völp, Jan Heering,
Volker Dötsch, Susanne Bösser, et al. “FAM96A Is a Novel Pro-Apoptotic Tumor Suppressor
in Gastrointestinal Stromal Tumors.” International Journal of Cancer. Wiley,
2015. https://doi.org/10.1002/ijc.29498.
ieee: B. Schwamb et al., “FAM96A is a novel pro-apoptotic tumor suppressor
in gastrointestinal stromal tumors,” International Journal of Cancer, vol.
137, no. 6. Wiley, pp. 1318–1329, 2015.
ista: Schwamb B, Pick R, Fernández S, Völp K, Heering J, Dötsch V, Bösser S, Jung
J, Beinoravičiute Kellner R, Wesely J, Zörnig I, Hammerschmidt M, Nowak M, Penzel
R, Zatloukal K, Joos S, Rieker R, Agaimy A, Söder S, Reid Lombardo K, Kendrick
M, Bardsley M, Hayashi Y, Asuzu D, Syed S, Ördög T, Zörnig M. 2015. FAM96A is
a novel pro-apoptotic tumor suppressor in gastrointestinal stromal tumors. International
Journal of Cancer. 137(6), 1318–1329.
mla: Schwamb, Bettina, et al. “FAM96A Is a Novel Pro-Apoptotic Tumor Suppressor
in Gastrointestinal Stromal Tumors.” International Journal of Cancer, vol.
137, no. 6, Wiley, 2015, pp. 1318–29, doi:10.1002/ijc.29498.
short: B. Schwamb, R. Pick, S. Fernández, K. Völp, J. Heering, V. Dötsch, S. Bösser,
J. Jung, R. Beinoravičiute Kellner, J. Wesely, I. Zörnig, M. Hammerschmidt, M.
Nowak, R. Penzel, K. Zatloukal, S. Joos, R. Rieker, A. Agaimy, S. Söder, K. Reid
Lombardo, M. Kendrick, M. Bardsley, Y. Hayashi, D. Asuzu, S. Syed, T. Ördög, M.
Zörnig, International Journal of Cancer 137 (2015) 1318–1329.
date_created: 2018-12-11T11:54:20Z
date_published: 2015-09-01T00:00:00Z
date_updated: 2021-01-12T06:53:36Z
day: '01'
department:
- _id: LifeSc
doi: 10.1002/ijc.29498
external_id:
pmid:
- '25716227'
intvolume: ' 137'
issue: '6'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497860/
month: '09'
oa: 1
oa_version: Submitted Version
page: 1318 - 1329
pmid: 1
publication: International Journal of Cancer
publication_status: published
publisher: Wiley
publist_id: '5253'
quality_controlled: '1'
scopus_import: 1
status: public
title: FAM96A is a novel pro-apoptotic tumor suppressor in gastrointestinal stromal
tumors
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 137
year: '2015'
...