Home > Publications database > Chronic spindle assembly checkpoint activation causes myelosuppression and gastrointestinal atrophy. > print

001     290533
005     20250514133124.0
024 7 _ |a 10.1038/s44319-024-00160-3
|2 doi
024 7 _ |a pmid:38806674
|2 pmid
024 7 _ |a 1469-221X
|2 ISSN
024 7 _ |a 1469-3178
|2 ISSN
024 7 _ |a altmetric:163924835
|2 altmetric
037 _ _ |a DKFZ-2024-01150
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Karbon, Gerlinde
|0 0000-0002-6149-3342
|b 0
245 _ _ |a Chronic spindle assembly checkpoint activation causes myelosuppression and gastrointestinal atrophy.
260 _ _ |a Hoboken, NJ [u.a.]
|c 2024
|b Wiley
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1718365064_3310
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
500 _ _ |a 2024 Jun;25(6):2743-2772
520 _ _ |a Interference with microtubule dynamics in mitosis activates the spindle assembly checkpoint (SAC) to prevent chromosome segregation errors. The SAC induces mitotic arrest by inhibiting the anaphase-promoting complex (APC) via the mitotic checkpoint complex (MCC). The MCC component MAD2 neutralizes the critical APC cofactor, CDC20, preventing exit from mitosis. Extended mitotic arrest can promote mitochondrial apoptosis and caspase activation. However, the impact of mitotic cell death on tissue homeostasis in vivo is ill-defined. By conditional MAD2 overexpression, we observe that chronic SAC activation triggers bone marrow aplasia and intestinal atrophy in mice. While myelosuppression can be compensated for, gastrointestinal atrophy is detrimental. Remarkably, deletion of pro-apoptotic Bim/Bcl2l11 prevents gastrointestinal syndrome, while neither loss of Noxa/Pmaip or co-deletion of Bid and Puma/Bbc3 has such a protective effect, identifying BIM as rate-limiting apoptosis effector in mitotic cell death of the gastrointestinal epithelium. In contrast, only overexpression of anti-apoptotic BCL2, but none of the BH3-only protein deficiencies mentioned above, can mitigate myelosuppression. Our findings highlight tissue and cell-type-specific survival dependencies in response to SAC perturbation in vivo.
536 _ _ |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312)
|0 G:(DE-HGF)POF4-312
|c POF4-312
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
650 _ 7 |a Apoptosis
|2 Other
650 _ 7 |a BH3-only Proteins
|2 Other
650 _ 7 |a MAD2
|2 Other
650 _ 7 |a Mitosis
|2 Other
650 _ 7 |a Spindle Assembly Checkpoint
|2 Other
700 1 _ |a Schuler, Fabian
|0 0000-0002-6407-2818
|b 1
700 1 _ |a Braun, Vincent Z
|0 0009-0006-0858-3775
|b 2
700 1 _ |a Eichin, Felix
|0 0000-0002-0085-1097
|b 3
700 1 _ |a Haschka, Manuel
|b 4
700 1 _ |a Drach, Mathias
|b 5
700 1 _ |a Sotillo, Rocio
|0 0000-0002-0855-7917
|b 6
700 1 _ |a Geley, Stephan
|b 7
700 1 _ |a Spierings, Diana Cj
|0 0000-0001-8403-474X
|b 8
700 1 _ |a Tijhuis, Andrea E
|0 0000-0001-8150-3061
|b 9
700 1 _ |a Foijer, Floris
|0 0000-0003-0989-3127
|b 10
700 1 _ |a Villunger, Andreas
|0 0000-0001-8259-4153
|b 11
773 _ _ |a 10.1038/s44319-024-00160-3
|0 PERI:(DE-600)2025376-X
|n 6
|p 2743-2772
|t EMBO reports
|v 25
|y 2024
|x 1469-221X
856 4 _ |u https://inrepo02.dkfz.de/record/290533/files/karbon-et-al-chronic-spindle-assembly-checkpoint-activation-causes-myelosuppression-and-gastrointestinal-atrophy.pdf
856 4 _ |u https://inrepo02.dkfz.de/record/290533/files/karbon-et-al-chronic-spindle-assembly-checkpoint-activation-causes-myelosuppression-and-gastrointestinal-atrophy.pdf?subformat=pdfa
|x pdfa
909 C O |p VDB
|o oai:inrepo02.dkfz.de:290533
910 1 _ |a Deutsches Krebsforschungszentrum
|0 I:(DE-588b)2036810-0
|k DKFZ
|b 6
|6 0000-0002-0855-7917
913 1 _ |a DE-HGF
|b Gesundheit
|l Krebsforschung
|1 G:(DE-HGF)POF4-310
|0 G:(DE-HGF)POF4-312
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Funktionelle und strukturelle Genomforschung
|x 0
914 1 _ |y 2024
915 _ _ |a DEAL Wiley
|0 StatID:(DE-HGF)3001
|2 StatID
|d 2023-10-24
|w ger
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b EMBO REP : 2022
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2023-10-24
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2023-10-24
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-10-24
915 _ _ |a IF >= 5
|0 StatID:(DE-HGF)9905
|2 StatID
|b EMBO REP : 2022
|d 2023-10-24
920 1 _ |0 I:(DE-He78)B220-20160331
|k B220
|l B220 Molekulare Grundlagen thorakaler Tumoren
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-He78)B220-20160331
980 _ _ |a UNRESTRICTED

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21