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@ARTICLE{Krver:138902,
author = {Körver, Lisa and Melzer, Juliane and Aguado Roca, Eva and
Teichert, Dominic and Glatter, Timo and Arama, Eli and
Broemer, Meike},
title = {{T}he de-ubiquitylating enzyme {DUBA} is essential for
spermatogenesis in {D}rosophila.},
journal = {Cell death and differentiation},
volume = {23},
number = {12},
issn = {1350-9047},
address = {London},
publisher = {Macmillan},
reportid = {DZNE-2020-05224},
pages = {2019-2030},
year = {2016},
abstract = {De-ubiquitylating enzymes (DUBs) reverse protein
ubiquitylation and thereby control essential cellular
functions. Screening for a DUB that counteracts caspase
ubiquitylation to regulate cell survival, we identified the
Drosophila ovarian tumour-type DUB DUBA (CG6091). DUBA
physically interacts with the initiator caspase death
regulator Nedd2-like caspase (Dronc) and de-ubiquitylates
it, thereby contributing to efficient inhibitor of
apoptosis-antagonist-induced apoptosis in the fly eye.
Searching also for non-apoptotic functions of DUBA, we found
that Duba-null mutants are male sterile and display defects
in spermatid individualisation, a process that depends on
non-apoptotic caspase activity. Spermatids of DUBA-deficient
flies showed reduced caspase activity and lack critical
structures of the individualisation process. Biochemical
characterisation revealed an obligate activation step of
DUBA by phosphorylation. With genetic rescue experiments we
demonstrate that DUBA phosphorylation and catalytic activity
are crucial in vivo for DUBA function in spermatogenesis.
Our results demonstrate for the first time the importance of
de-ubiquitylation for fly spermatogenesis.},
keywords = {Amino Acid Sequence / Animals / Apoptosis / Biocatalysis /
Caspases: metabolism / Deubiquitinating Enzymes: chemistry /
Deubiquitinating Enzymes: metabolism / Drosophila Proteins:
chemistry / Drosophila Proteins: metabolism / Drosophila
melanogaster: enzymology / Drosophila melanogaster:
physiology / Male / Phosphorylation / Phosphoserine:
metabolism / Protein Binding / Spermatogenesis / Testis:
metabolism / Ubiquitinated Proteins: metabolism /
Ubiquitination / Drosophila Proteins (NLM Chemicals) /
Ubiquitinated Proteins (NLM Chemicals) / Phosphoserine (NLM
Chemicals) / DUBA protein, Drosophila (NLM Chemicals) /
Deubiquitinating Enzymes (NLM Chemicals) / Caspases (NLM
Chemicals)},
cin = {AG Brömer 2 / AG Brömer 1},
ddc = {610},
cid = {I:(DE-2719)1013021 / I:(DE-2719)5000021},
pnm = {341 - Molecular Signaling (POF3-341)},
pid = {G:(DE-HGF)POF3-341},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27518434},
pmc = {pmc:PMC5136489},
doi = {10.1038/cdd.2016.79},
url = {https://pub.dzne.de/record/138902},
}