Article (Scientific journals)
Interactome network analysis identifies multiple caspase-6 interactors involved in the pathogenesis of HD.
Riechers, Sean-Patrick Hermann; Butland, Stefanie; Deng, Yu et al.
2016In Human Molecular Genetics, 25 (8), p. 1600-18
Peer Reviewed verified by ORBi


Full Text
Publisher postprint (1.26 MB)

All documents in ORBilu are protected by a user license.

Send to


Keywords :
Binding Sites; Caspase 6/metabolism; Cell Line; Gene Expression Regulation; Humans; Huntingtin Protein/genetics; Huntington Disease/metabolism/pathology; Models, Biological; Protein Interaction Maps; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases/metabolism; Serine-Threonine Kinase 3; Two-Hybrid System Techniques
Abstract :
[en] Caspase-6 (CASP6) has emerged as an important player in Huntington disease (HD), Alzheimer disease (AD) and cerebral ischemia, where it is activated early in the disease process. CASP6 also plays a key role in axonal degeneration, further underscoring the importance of this protease in neurodegenerative pathways. As a protein's function is modulated by its protein-protein interactions, we performed a high-throughput yeast-2-hybrid (Y2H) screen against ∼17,000 human proteins to gain further insight into the function of CASP6. We identified a high-confidence list of 87 potential CASP6 interactors. From this list, 61% are predicted to contain a CASP6 recognition site. Of nine candidate substrates assessed, six are cleaved by CASP6. Proteins that did not contain a predicted CASP6 recognition site were assessed using a LUMIER assay approach, and 51% were further validated as interactors by this method. Of note, 54% of the high-confidence interactors identified show alterations in human HD brain at the mRNA level, and there is a significant enrichment for previously validated huntingtin (HTT) interactors. One protein of interest, STK3, a pro-apoptotic kinase, was validated biochemically to be a CASP6 substrate. Furthermore, our results demonstrate that in striatal cells expressing mutant huntingtin (mHTT), an increase in full length and fragment levels of STK3 are observed. We further show that caspase-3 is not essential for the endogenous cleavage of STK3. Characterization of the interaction network provides important new information regarding key pathways of interactors of CASP6 and highlights potential novel therapeutic targets for HD, AD and cerebral ischemia.
Disciplines :
Author, co-author :
Riechers, Sean-Patrick Hermann  ;  Max Delbrück Centrum für Molekulare Medizin Berlin-Buch, Neuroproteomics, Berlin 13125, Germany.
Butland, Stefanie
Deng, Yu
Skotte, Niels
Ehrnhoefer, Dagmar E.
Russ, Jenny
Laine, Jean
Laroche, Melissa
Pouladi, Mahmoud A.
Wanker, Erich E.
Hayden, Michael R.
Graham, Rona K.
External co-authors :
Language :
Title :
Interactome network analysis identifies multiple caspase-6 interactors involved in the pathogenesis of HD.
Publication date :
Journal title :
Human Molecular Genetics
Publisher :
Oxford University Press, United Kingdom
Volume :
Issue :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email:
Available on ORBilu :
since 12 September 2023


Number of views
22 (1 by Unilu)
Number of downloads
3 (0 by Unilu)

WoS citations


Similar publications

Contact ORBilu