TY  - JOUR
AU  - Körver, Lisa
AU  - Melzer, Juliane
AU  - Aguado Roca, Eva
AU  - Teichert, Dominic
AU  - Glatter, Timo
AU  - Arama, Eli
AU  - Broemer, Meike
TI  - The de-ubiquitylating enzyme DUBA is essential for spermatogenesis in Drosophila.
JO  - Cell death and differentiation
VL  - 23
IS  - 12
SN  - 1350-9047
CY  - London
PB  - Macmillan
M1  - DZNE-2020-05224
SP  - 2019-2030
PY  - 2016
AB  - 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.
KW  - Amino Acid Sequence
KW  - Animals
KW  - Apoptosis
KW  - Biocatalysis
KW  - Caspases: metabolism
KW  - Deubiquitinating Enzymes: chemistry
KW  - Deubiquitinating Enzymes: metabolism
KW  - Drosophila Proteins: chemistry
KW  - Drosophila Proteins: metabolism
KW  - Drosophila melanogaster: enzymology
KW  - Drosophila melanogaster: physiology
KW  - Male
KW  - Phosphorylation
KW  - Phosphoserine: metabolism
KW  - Protein Binding
KW  - Spermatogenesis
KW  - Testis: metabolism
KW  - Ubiquitinated Proteins: metabolism
KW  - Ubiquitination
KW  - Drosophila Proteins (NLM Chemicals)
KW  - Ubiquitinated Proteins (NLM Chemicals)
KW  - Phosphoserine (NLM Chemicals)
KW  - DUBA protein, Drosophila (NLM Chemicals)
KW  - Deubiquitinating Enzymes (NLM Chemicals)
KW  - Caspases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27518434
C2  - pmc:PMC5136489
DO  - DOI:10.1038/cdd.2016.79
UR  - https://pub.dzne.de/record/138902
ER  -