---
_id: '11160'
abstract:
- lang: eng
  text: Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent
    cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses
    macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency
    affects neurodevelopmental is unclear. Here, employing human cerebral organoids,
    we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories
    with an accelerated and delayed generation of, respectively, inhibitory and excitatory
    neurons that yields, at days 60 and 120, symmetrically opposite expansions in
    their proportions. This imbalance is consistent with an enlargement of cerebral
    organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic
    design of patient-specific mutations and mosaic organoids, we define genotype-phenotype
    relationships and uncover their cell-autonomous nature. Our results define cell-type-specific
    CHD8-dependent molecular defects related to an abnormal program of proliferation
    and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations,
    our study uncovers reproducible developmental alterations that may be employed
    for neurodevelopmental disease modeling.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
acknowledgement: We thank Farnaz Freeman for technical assistance. This research was
  supported by the Scientific Service Units (SSU) of IST Austria through resources
  provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This
  work supported by the European Union’s Horizon 2020 research and innovation program
  (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs);
  the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele;
  and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures
  were created using BioRender.com.
article_number: '110615'
article_processing_charge: Yes
article_type: original
author:
- first_name: Carlo Emanuele
  full_name: Villa, Carlo Emanuele
  last_name: Villa
- first_name: Cristina
  full_name: Cheroni, Cristina
  last_name: Cheroni
- first_name: Christoph
  full_name: Dotter, Christoph
  id: 4C66542E-F248-11E8-B48F-1D18A9856A87
  last_name: Dotter
  orcid: 0000-0002-9033-9096
- first_name: Alejandro
  full_name: López-Tóbon, Alejandro
  last_name: López-Tóbon
- first_name: Bárbara
  full_name: Oliveira, Bárbara
  id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87
  last_name: Oliveira
- first_name: Roberto
  full_name: Sacco, Roberto
  id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
  last_name: Sacco
- first_name: Aysan Çerağ
  full_name: Yahya, Aysan Çerağ
  id: 365A65F8-F248-11E8-B48F-1D18A9856A87
  last_name: Yahya
- first_name: Jasmin
  full_name: Morandell, Jasmin
  id: 4739D480-F248-11E8-B48F-1D18A9856A87
  last_name: Morandell
- first_name: Michele
  full_name: Gabriele, Michele
  last_name: Gabriele
- first_name: Mojtaba
  full_name: Tavakoli, Mojtaba
  id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
  last_name: Tavakoli
  orcid: 0000-0002-7667-6854
- first_name: Julia
  full_name: Lyudchik, Julia
  id: 46E28B80-F248-11E8-B48F-1D18A9856A87
  last_name: Lyudchik
- first_name: Christoph M
  full_name: Sommer, Christoph M
  id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
  last_name: Sommer
  orcid: 0000-0003-1216-9105
- first_name: Mariano
  full_name: Gabitto, Mariano
  last_name: Gabitto
- first_name: Johann G
  full_name: Danzl, Johann G
  id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
  last_name: Danzl
  orcid: 0000-0001-8559-3973
- first_name: Giuseppe
  full_name: Testa, Giuseppe
  last_name: Testa
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism
    to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>.
    2022;39(1). doi:<a href="https://doi.org/10.1016/j.celrep.2022.110615">10.1016/j.celrep.2022.110615</a>
  apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco,
    R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations
    in excitatory and inhibitory trajectories. <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2022.110615">https://doi.org/10.1016/j.celrep.2022.110615</a>
  chicago: Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon,
    Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency
    Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.”
    <i>Cell Reports</i>. Elsevier, 2022. <a href="https://doi.org/10.1016/j.celrep.2022.110615">https://doi.org/10.1016/j.celrep.2022.110615</a>.
  ieee: C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient
    alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol.
    39, no. 1. Elsevier, 2022.
  ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ,
    Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG,
    Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations
    in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.
  mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient
    Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol.
    39, no. 1, 110615, Elsevier, 2022, doi:<a href="https://doi.org/10.1016/j.celrep.2022.110615">10.1016/j.celrep.2022.110615</a>.
  short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco,
    A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer,
    M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).
corr_author: '1'
date_created: 2022-04-15T09:03:10Z
date_published: 2022-04-05T00:00:00Z
date_updated: 2026-05-30T22:30:37Z
day: '05'
ddc:
- '570'
department:
- _id: JoDa
- _id: GaNo
doi: 10.1016/j.celrep.2022.110615
ec_funded: 1
external_id:
  isi:
  - '000785983900003'
  pmid:
  - '35385734'
file:
- access_level: open_access
  checksum: b4e8d68f0268dec499af333e6fd5d8e1
  content_type: application/pdf
  creator: dernst
  date_created: 2022-04-15T09:06:25Z
  date_updated: 2022-04-15T09:06:25Z
  file_id: '11164'
  file_name: 2022_CellReports_Villa.pdf
  file_size: '7808644'
  relation: main_file
  success: 1
file_date_updated: 2022-04-15T09:06:25Z
has_accepted_license: '1'
intvolume: '        39'
isi: 1
issue: '1'
keyword:
- General Biochemistry
- Genetics and Molecular Biology
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
- _id: 2690FEAC-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: I04205
  name: Identification of converging Molecular Pathways Across Chromatinopathies as
    Targets for Therapy
publication: Cell Reports
publication_identifier:
  issn:
  - 2211-1247
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  record:
  - id: '18681'
    relation: dissertation_contains
    status: public
  - id: '18674'
    relation: dissertation_contains
    status: public
  - id: '12364'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: CHD8 haploinsufficiency links autism to transient alterations in excitatory
  and inhibitory trajectories
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 39
year: '2022'
...
---
_id: '546'
abstract:
- lang: eng
  text: The precise control of neural stem cell (NSC) proliferation and differentiation
    is crucial for the development and function of the human brain. Here, we review
    the emerging links between the alteration of embryonic and adult neurogenesis
    and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum
    disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based
    modeling and the novel therapeutic targets derived from these studies.
article_processing_charge: No
author:
- first_name: Roberto
  full_name: Sacco, Roberto
  id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
  last_name: Sacco
- first_name: Emanuele
  full_name: Cacci, Emanuele
  last_name: Cacci
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: Sacco R, Cacci E, Novarino G. Neural stem cells in neuropsychiatric disorders.
    <i>Current Opinion in Neurobiology</i>. 2018;48(2):131-138. doi:<a href="https://doi.org/10.1016/j.conb.2017.12.005">10.1016/j.conb.2017.12.005</a>
  apa: Sacco, R., Cacci, E., &#38; Novarino, G. (2018). Neural stem cells in neuropsychiatric
    disorders. <i>Current Opinion in Neurobiology</i>. Elsevier. <a href="https://doi.org/10.1016/j.conb.2017.12.005">https://doi.org/10.1016/j.conb.2017.12.005</a>
  chicago: Sacco, Roberto, Emanuele Cacci, and Gaia Novarino. “Neural Stem Cells in
    Neuropsychiatric Disorders.” <i>Current Opinion in Neurobiology</i>. Elsevier,
    2018. <a href="https://doi.org/10.1016/j.conb.2017.12.005">https://doi.org/10.1016/j.conb.2017.12.005</a>.
  ieee: R. Sacco, E. Cacci, and G. Novarino, “Neural stem cells in neuropsychiatric
    disorders,” <i>Current Opinion in Neurobiology</i>, vol. 48, no. 2. Elsevier,
    pp. 131–138, 2018.
  ista: Sacco R, Cacci E, Novarino G. 2018. Neural stem cells in neuropsychiatric
    disorders. Current Opinion in Neurobiology. 48(2), 131–138.
  mla: Sacco, Roberto, et al. “Neural Stem Cells in Neuropsychiatric Disorders.” <i>Current
    Opinion in Neurobiology</i>, vol. 48, no. 2, Elsevier, 2018, pp. 131–38, doi:<a
    href="https://doi.org/10.1016/j.conb.2017.12.005">10.1016/j.conb.2017.12.005</a>.
  short: R. Sacco, E. Cacci, G. Novarino, Current Opinion in Neurobiology 48 (2018)
    131–138.
corr_author: '1'
date_created: 2018-12-11T11:47:06Z
date_published: 2018-02-01T00:00:00Z
date_updated: 2024-10-09T20:58:31Z
day: '01'
department:
- _id: GaNo
doi: 10.1016/j.conb.2017.12.005
external_id:
  isi:
  - '000427101600018'
intvolume: '        48'
isi: 1
issue: '2'
language:
- iso: eng
month: '02'
oa_version: None
page: 131 - 138
publication: Current Opinion in Neurobiology
publication_status: published
publisher: Elsevier
publist_id: '7268'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Neural stem cells in neuropsychiatric disorders
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 48
year: '2018'
...
---
_id: '1228'
abstract:
- lang: eng
  text: Since 2006, reprogrammed cells have increasingly been used as a biomedical
    research technique in addition to neuro-psychiatric methods. These rapidly evolving
    techniques allow for the generation of neuronal sub-populations, and have sparked
    interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic
    and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder
    (BPD). This review provides a summary of 19 publications on reprogrammed adult
    somatic cells derived from patients with SCZ, and five publications using this
    technique in patients with BPD. As both disorders are complex and heterogeneous,
    there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations
    of dopaminergic transmission in vitro are sparse, despite the great explanatory
    power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations
    of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental
    alterations. Some studies also report on the efficacy of medicinal compounds to
    revert alterations observed in cellular models. However, due to the paucity of
    replication studies, no comprehensive conclusions can be drawn from studies using
    reprogrammed cells at the present time. In the future, findings from cell culture
    methods need to be integrated with clinical, epidemiological, pharmacological
    and imaging data in order to generate a more comprehensive picture of SCZ and
    BPD.
acknowledgement: This work was supported by grants of the Austrian Science Fund (FWF)
  P23585B09 to M.W. and F3506 to H.H.S. and the “Wiener Wissenschafts-, Forschungs-
  und Technologiefonds” (Vienna Science and Technology Fund; WWTF) CS15-033 to M.W.
article_processing_charge: No
article_type: review
author:
- first_name: Ulrich
  full_name: Sauerzopf, Ulrich
  last_name: Sauerzopf
- first_name: Roberto
  full_name: Sacco, Roberto
  id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
  last_name: Sacco
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
- first_name: Marco
  full_name: Niello, Marco
  last_name: Niello
- first_name: Ana
  full_name: Weidenauer, Ana
  last_name: Weidenauer
- first_name: Nicole
  full_name: Praschak Rieder, Nicole
  last_name: Praschak Rieder
- first_name: Harald
  full_name: Sitte, Harald
  last_name: Sitte
- first_name: Matthaeus
  full_name: Willeit, Matthaeus
  last_name: Willeit
citation:
  ama: Sauerzopf U, Sacco R, Novarino G, et al. Are reprogrammed cells a useful tool
    for studying dopamine dysfunction in psychotic disorders? A review of the current
    evidence. <i>European Journal of Neuroscience</i>. 2017;45(1):45-57. doi:<a href="https://doi.org/10.1111/ejn.13418">10.1111/ejn.13418</a>
  apa: Sauerzopf, U., Sacco, R., Novarino, G., Niello, M., Weidenauer, A., Praschak
    Rieder, N., … Willeit, M. (2017). Are reprogrammed cells a useful tool for studying
    dopamine dysfunction in psychotic disorders? A review of the current evidence.
    <i>European Journal of Neuroscience</i>. Wiley-Blackwell. <a href="https://doi.org/10.1111/ejn.13418">https://doi.org/10.1111/ejn.13418</a>
  chicago: Sauerzopf, Ulrich, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer,
    Nicole Praschak Rieder, Harald Sitte, and Matthaeus Willeit. “Are Reprogrammed
    Cells a Useful Tool for Studying Dopamine Dysfunction in Psychotic Disorders?
    A Review of the Current Evidence.” <i>European Journal of Neuroscience</i>. Wiley-Blackwell,
    2017. <a href="https://doi.org/10.1111/ejn.13418">https://doi.org/10.1111/ejn.13418</a>.
  ieee: U. Sauerzopf <i>et al.</i>, “Are reprogrammed cells a useful tool for studying
    dopamine dysfunction in psychotic disorders? A review of the current evidence,”
    <i>European Journal of Neuroscience</i>, vol. 45, no. 1. Wiley-Blackwell, pp.
    45–57, 2017.
  ista: Sauerzopf U, Sacco R, Novarino G, Niello M, Weidenauer A, Praschak Rieder
    N, Sitte H, Willeit M. 2017. Are reprogrammed cells a useful tool for studying
    dopamine dysfunction in psychotic disorders? A review of the current evidence.
    European Journal of Neuroscience. 45(1), 45–57.
  mla: Sauerzopf, Ulrich, et al. “Are Reprogrammed Cells a Useful Tool for Studying
    Dopamine Dysfunction in Psychotic Disorders? A Review of the Current Evidence.”
    <i>European Journal of Neuroscience</i>, vol. 45, no. 1, Wiley-Blackwell, 2017,
    pp. 45–57, doi:<a href="https://doi.org/10.1111/ejn.13418">10.1111/ejn.13418</a>.
  short: U. Sauerzopf, R. Sacco, G. Novarino, M. Niello, A. Weidenauer, N. Praschak
    Rieder, H. Sitte, M. Willeit, European Journal of Neuroscience 45 (2017) 45–57.
date_created: 2018-12-11T11:50:50Z
date_published: 2017-01-01T00:00:00Z
date_updated: 2023-09-20T11:16:01Z
day: '01'
ddc:
- '616'
department:
- _id: GaNo
doi: 10.1111/ejn.13418
external_id:
  isi:
  - '000392487100005'
  pmid:
  - '27690184'
file:
- access_level: open_access
  checksum: c572cf02be8fbb7020cfcfb892182e4c
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:10:48Z
  date_updated: 2020-07-14T12:44:39Z
  file_id: '4838'
  file_name: IST-2017-738-v1+1_Sauerzopf_et_al-2017-European_Journal_of_Neuroscience.pdf
  file_size: 169145
  relation: main_file
file_date_updated: 2020-07-14T12:44:39Z
has_accepted_license: '1'
intvolume: '        45'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 45 - 57
pmid: 1
publication: European Journal of Neuroscience
publication_status: published
publisher: Wiley-Blackwell
publist_id: '6106'
pubrep_id: '738'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic
  disorders? A review of the current evidence
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 45
year: '2017'
...
---
_id: '540'
abstract:
- lang: eng
  text: RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of
    RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis
    virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection.
    A major genetic determinant for its ability to persist maps to a single amino
    acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional
    consequences remain elusive. To unravel the L protein interactions with the host
    proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics.
    A subsequent mass-spectrometric analysis of L protein pulldowns from infected
    human cells revealed a comprehensive network of interacting host proteins. The
    obtained LCMV L protein interactome was bioinformatically integrated with known
    host protein interactors of RdRps from other RNA viruses, emphasizing interconnected
    modules of human proteins. Functional characterization of selected interactors
    highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors.
    To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired
    virus control in chronic infection. These results provide insights into the complex
    interactions of the arenavirus LCMV and other viral RdRps with the host proteome
    and contribute to a better molecular understanding of how chronic viruses interact
    with their host.
article_number: e1006758
article_processing_charge: No
author:
- first_name: Kseniya
  full_name: Khamina, Kseniya
  last_name: Khamina
- first_name: Alexander
  full_name: Lercher, Alexander
  last_name: Lercher
- first_name: Michael
  full_name: Caldera, Michael
  last_name: Caldera
- first_name: Christopher
  full_name: Schliehe, Christopher
  last_name: Schliehe
- first_name: Bojan
  full_name: Vilagos, Bojan
  last_name: Vilagos
- first_name: Mehmet
  full_name: Sahin, Mehmet
  last_name: Sahin
- first_name: Lindsay
  full_name: Kosack, Lindsay
  last_name: Kosack
- first_name: Anannya
  full_name: Bhattacharya, Anannya
  last_name: Bhattacharya
- first_name: Peter
  full_name: Májek, Peter
  last_name: Májek
- first_name: Alexey
  full_name: Stukalov, Alexey
  last_name: Stukalov
- first_name: Roberto
  full_name: Sacco, Roberto
  id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
  last_name: Sacco
- first_name: Leo
  full_name: James, Leo
  last_name: James
- first_name: Daniel
  full_name: Pinschewer, Daniel
  last_name: Pinschewer
- first_name: Keiryn
  full_name: Bennett, Keiryn
  last_name: Bennett
- first_name: Jörg
  full_name: Menche, Jörg
  last_name: Menche
- first_name: Andreas
  full_name: Bergthaler, Andreas
  last_name: Bergthaler
citation:
  ama: Khamina K, Lercher A, Caldera M, et al. Characterization of host proteins interacting
    with the lymphocytic choriomeningitis virus L protein. <i>PLoS Pathogens</i>.
    2017;13(12). doi:<a href="https://doi.org/10.1371/journal.ppat.1006758">10.1371/journal.ppat.1006758</a>
  apa: Khamina, K., Lercher, A., Caldera, M., Schliehe, C., Vilagos, B., Sahin, M.,
    … Bergthaler, A. (2017). Characterization of host proteins interacting with the
    lymphocytic choriomeningitis virus L protein. <i>PLoS Pathogens</i>. Public Library
    of Science. <a href="https://doi.org/10.1371/journal.ppat.1006758">https://doi.org/10.1371/journal.ppat.1006758</a>
  chicago: Khamina, Kseniya, Alexander Lercher, Michael Caldera, Christopher Schliehe,
    Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, et al. “Characterization of Host
    Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” <i>PLoS
    Pathogens</i>. Public Library of Science, 2017. <a href="https://doi.org/10.1371/journal.ppat.1006758">https://doi.org/10.1371/journal.ppat.1006758</a>.
  ieee: K. Khamina <i>et al.</i>, “Characterization of host proteins interacting with
    the lymphocytic choriomeningitis virus L protein,” <i>PLoS Pathogens</i>, vol.
    13, no. 12. Public Library of Science, 2017.
  ista: Khamina K, Lercher A, Caldera M, Schliehe C, Vilagos B, Sahin M, Kosack L,
    Bhattacharya A, Májek P, Stukalov A, Sacco R, James L, Pinschewer D, Bennett K,
    Menche J, Bergthaler A. 2017. Characterization of host proteins interacting with
    the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 13(12), e1006758.
  mla: Khamina, Kseniya, et al. “Characterization of Host Proteins Interacting with
    the Lymphocytic Choriomeningitis Virus L Protein.” <i>PLoS Pathogens</i>, vol.
    13, no. 12, e1006758, Public Library of Science, 2017, doi:<a href="https://doi.org/10.1371/journal.ppat.1006758">10.1371/journal.ppat.1006758</a>.
  short: K. Khamina, A. Lercher, M. Caldera, C. Schliehe, B. Vilagos, M. Sahin, L.
    Kosack, A. Bhattacharya, P. Májek, A. Stukalov, R. Sacco, L. James, D. Pinschewer,
    K. Bennett, J. Menche, A. Bergthaler, PLoS Pathogens 13 (2017).
date_created: 2018-12-11T11:47:03Z
date_published: 2017-12-01T00:00:00Z
date_updated: 2025-09-18T09:43:05Z
day: '01'
ddc:
- '576'
- '616'
department:
- _id: GaNo
doi: 10.1371/journal.ppat.1006758
external_id:
  isi:
  - '000419019800019'
file:
- access_level: open_access
  checksum: 1aa20f19a1e90664fadce6e7d5284fdc
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:12:26Z
  date_updated: 2020-07-14T12:46:44Z
  file_id: '4944'
  file_name: IST-2018-931-v1+1_journal.ppat.1006758.pdf
  file_size: 4106772
  relation: main_file
file_date_updated: 2020-07-14T12:46:44Z
has_accepted_license: '1'
intvolume: '        13'
isi: 1
issue: '12'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
publication: PLoS Pathogens
publication_identifier:
  issn:
  - 1553-7366
publication_status: published
publisher: Public Library of Science
publist_id: '7276'
pubrep_id: '931'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Characterization of host proteins interacting with the lymphocytic choriomeningitis
  virus L protein
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 13
year: '2017'
...
---
OA_place: publisher
OA_type: hybrid
_id: '460'
abstract:
- lang: eng
  text: NF-κB signaling is a central pathway of immunity and integrates signal transduction
    upon a wide array of inflammatory stimuli. Noncanonical NF-κB signaling is activated
    by a small subset of TNF family receptors and characterized by NF-κB2/p52 transcriptional
    activity. The medical relevance of this pathway has recently re-emerged from the
    discovery of primary immunodeficiency patients that have loss-of-function mutations
    in the MAP3K14 gene encoding NIK. Nevertheless, knowledge of protein interactions
    that regulate noncanonical NF-κB signaling is sparse. Here we report a detailed
    state-of-the-art mass spectrometry-based protein–protein interaction network including
    the noncanonical NF-κB signaling nodes TRAF2, TRAF3, IKKα, NIK, and NF-κB2/p100.
    The value of the data set was confirmed by the identification of interactions
    already known to regulate this pathway. In addition, a remarkable number of novel
    interactors were identified. We provide validation of the novel NIK and IKKα interactor
    FKBP8, which may regulate processes downstream of noncanonical NF-κB signaling.
    To understand perturbed noncanonical NF-κB signaling in the context of misregulated
    NIK in disease, we also provide a differential interactome of NIK mutants that
    cause immunodeficiency. Altogether, this data set not only provides critical insight
    into how protein–protein interactions can regulate immune signaling but also offers
    a novel resource on noncanonical NF-κB signaling.
acknowledgement: "Austrian Science Fund (FWF) Lise Meitner Program Fellowship (FWF
  M-1809, to K.L.W.),  FWF Infect-ERA framework (I-1620_B22, to S.K.), European Research
  Council (ERC StG 310857, to K.B.)\r\nWe thank Jacques Colinge, André C. Müller,
  and Peter Májek for fruitful discussions and Elisabeth Salzer and Kate G. Ackermann
  for critically reading the manuscript. We thank Giulio Superti-Furga for providing
  pTO-SII-HA-GW plasmids. \r\n\r\n"
article_processing_charge: No
article_type: original
author:
- first_name: Katharina
  full_name: Willmann, Katharina
  last_name: Willmann
- first_name: Roberto
  full_name: Sacco, Roberto
  id: 42C9F57E-F248-11E8-B48F-1D18A9856A87
  last_name: Sacco
- first_name: Rui
  full_name: Martins, Rui
  last_name: Martins
- first_name: Wojciech
  full_name: Garncarz, Wojciech
  last_name: Garncarz
- first_name: Ana
  full_name: Krolo, Ana
  last_name: Krolo
- first_name: Sylvia
  full_name: Knapp, Sylvia
  last_name: Knapp
- first_name: Keiryn
  full_name: Bennett, Keiryn
  last_name: Bennett
- first_name: Kaan
  full_name: Boztug, Kaan
  last_name: Boztug
citation:
  ama: Willmann K, Sacco R, Martins R, et al. Expanding the interactome of the noncanonical
    NF-κB signaling pathway. <i>Journal of Proteome Research</i>. 2016;15(9):2900-2909.
    doi:<a href="https://doi.org/10.1021/acs.jproteome.5b01004">10.1021/acs.jproteome.5b01004</a>
  apa: Willmann, K., Sacco, R., Martins, R., Garncarz, W., Krolo, A., Knapp, S., …
    Boztug, K. (2016). Expanding the interactome of the noncanonical NF-κB signaling
    pathway. <i>Journal of Proteome Research</i>. American Chemical Society. <a href="https://doi.org/10.1021/acs.jproteome.5b01004">https://doi.org/10.1021/acs.jproteome.5b01004</a>
  chicago: Willmann, Katharina, Roberto Sacco, Rui Martins, Wojciech Garncarz, Ana
    Krolo, Sylvia Knapp, Keiryn Bennett, and Kaan Boztug. “Expanding the Interactome
    of the Noncanonical NF-ΚB Signaling Pathway.” <i>Journal of Proteome Research</i>.
    American Chemical Society, 2016. <a href="https://doi.org/10.1021/acs.jproteome.5b01004">https://doi.org/10.1021/acs.jproteome.5b01004</a>.
  ieee: K. Willmann <i>et al.</i>, “Expanding the interactome of the noncanonical
    NF-κB signaling pathway,” <i>Journal of Proteome Research</i>, vol. 15, no. 9.
    American Chemical Society, pp. 2900–2909, 2016.
  ista: Willmann K, Sacco R, Martins R, Garncarz W, Krolo A, Knapp S, Bennett K, Boztug
    K. 2016. Expanding the interactome of the noncanonical NF-κB signaling pathway.
    Journal of Proteome Research. 15(9), 2900–2909.
  mla: Willmann, Katharina, et al. “Expanding the Interactome of the Noncanonical
    NF-ΚB Signaling Pathway.” <i>Journal of Proteome Research</i>, vol. 15, no. 9,
    American Chemical Society, 2016, pp. 2900–09, doi:<a href="https://doi.org/10.1021/acs.jproteome.5b01004">10.1021/acs.jproteome.5b01004</a>.
  short: K. Willmann, R. Sacco, R. Martins, W. Garncarz, A. Krolo, S. Knapp, K. Bennett,
    K. Boztug, Journal of Proteome Research 15 (2016) 2900–2909.
date_created: 2018-12-11T11:46:36Z
date_published: 2016-09-02T00:00:00Z
date_updated: 2026-05-12T12:34:04Z
day: '02'
doi: 10.1021/acs.jproteome.5b01004
extern: '1'
external_id:
  pmid:
  - '27416764'
intvolume: '        15'
issue: '9'
keyword:
- noncanonical NF-κB signaling
- tandem affinity purification
- protein−protein interaction network
- NF-κB inducing kinase
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://doi.org/10.1021/acs.jproteome.5b01004
month: '09'
oa: 1
oa_version: Published Version
page: 2900 - 2909
pmid: 1
publication: Journal of Proteome Research
publication_identifier:
  eissn:
  - 1535-3907
  issn:
  - 1535-3893
publication_status: published
publisher: American Chemical Society
publist_id: '7361'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Expanding the interactome of the noncanonical NF-κB signaling pathway
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 15
year: '2016'
...