Journal Article

DZNE-2020-05224

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The de-ubiquitylating enzyme DUBA is essential for spermatogenesis in Drosophila.

Körver, L. (First author)DZNE* ; Melzer, J.DZNE* ; Aguado Roca, E.DZNE* ; Teichert, D.DZNE* ; Glatter, T. ; Arama, E. ; Broemer, M. (Last author)DZNE*

2016
Macmillan London

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Please use a persistent id in citations: doi:10.1038/cdd.2016.79

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.

Keyword(s): Amino Acid Sequence (MeSH) ; Animals (MeSH) ; Apoptosis (MeSH) ; Biocatalysis (MeSH) ; Caspases: metabolism (MeSH) ; Deubiquitinating Enzymes: chemistry (MeSH) ; Deubiquitinating Enzymes: metabolism (MeSH) ; Drosophila Proteins: chemistry (MeSH) ; Drosophila Proteins: metabolism (MeSH) ; Drosophila melanogaster: enzymology (MeSH) ; Drosophila melanogaster: physiology (MeSH) ; Male (MeSH) ; Phosphorylation (MeSH) ; Phosphoserine: metabolism (MeSH) ; Protein Binding (MeSH) ; Spermatogenesis (MeSH) ; Testis: metabolism (MeSH) ; Ubiquitinated Proteins: metabolism (MeSH) ; Ubiquitination (MeSH) ; Drosophila Proteins ; Ubiquitinated Proteins ; Phosphoserine ; DUBA protein, Drosophila ; Deubiquitinating Enzymes ; Caspases

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Contributing Institute(s):

1. AG Brömer (AG Brömer 2)
2. Ubiquitin-mediated Processes in Neurodegenerative Diseases (AG Brömer 1)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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