Altered expression of CG5961, a putative Drosophila melanogaster homologue of FBXO9, provides a new model of Parkinson disease

Abstract

ABSTRACT. F-box proteins act as the protein recognition component of the Skp-Cul-F-box class of ubiquitin ligases. Two members of a gene sub-family encoding these proteins, FBXO7 and FBXO32, have been implicated in the onset and progression of degenerative disease. FBXO7 is responsible for rare genetic forms of Parkinson disease, while FBXO32 has been implicated in muscle wasting. The third gene in this family, FBXO9, is related to growth signaling, but the role of this gene in degenerative disease pathways has not been thoroughly investigated. Characterizing the putative Drosophila melanogaster homologue of this gene, CG5961, enables modeling and analysis of the consequence of targeted alteration of gene function and the effects on the overall health of the organism. or CG5961-RNAi in the dopaminergic neurons led to a reduced lifespan compared to that in lacZ controls. We showed that protein structures of CG5961 and FBXO9 are highly similar and studied the effects of altered expression of CG5961 in neuron-rich tissues. Our results suggest that CG5961 activity is necessary for the proper formation of neuronal tissue and that targeted alteration of gene expression in dopaminergic neurons leads to a reduced lifespan.

Integration of gene co-expression analysis and multi-class SVM specifies the functional players involved in determining the fate of HTLV-1 infection toward the development of cancer (ATLL) or neurological disorder (HAM/TSP)

“…FBXO9 belongs to the F-box protein family , which constitutes one of the subunits of the ubiquitin -protein ligase complex. The possible association of FBXO9 and degenerative disease phenotypes and also the involvement in the development of neuronal disorders have been reported [ 64 ]. However, its functional role in HAM/TSP should be further investigated.…”