The Drosophila orthologue of the INT6 onco-protein regulates mitotic microtubule growth and kinetochore structure

PLoS Genetics
Fioranna RendaMaria Patrizia Somma

Abstract

INT6/eIF3e is a highly conserved component of the translation initiation complex that interacts with both the 26S proteasome and the COP9 signalosome, two complexes implicated in ubiquitin-mediated protein degradation. The INT6 gene was originally identified as the insertion site of the mouse mammary tumor virus (MMTV), and later shown to be involved in human tumorigenesis. Here we show that depletion of the Drosophila orthologue of INT6 (Int6) results in short mitotic spindles and deformed centromeres and kinetochores with low intra-kinetochore distance. Poleward flux of microtubule subunits during metaphase is reduced, although fluorescence recovery after photobleaching (FRAP) demonstrates that microtubules remain dynamic both near the kinetochores and at spindle poles. Mitotic progression is delayed during metaphase due to the activity of the spindle assembly checkpoint (SAC). Interestingly, a deubiquitinated form of the kinesin Klp67A (a putative orthologue of human Kif18A) accumulates near the kinetochores in Int6-depleted cells. Consistent with this finding, Klp67A overexpression mimics the Int6 RNAi phenotype. Furthermore, simultaneous depletion of Int6 and Klp67A results in a phenotype identical to RNAi of just Klp67A, ...Continue Reading

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Citations

Nov 27, 2018·ELife·Claudia PellacaniMaria Patrizia Somma
Jul 10, 2019·BMC Molecular and Cell Biology·Gera A PavlovaAlexey V Pindyurin
Mar 31, 2021·Seminars in Cell & Developmental Biology·J Richard McIntosh
Jun 1, 2021·Seminars in Cell & Developmental Biology·Marin BarisicYulia Steblyanko

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Methods Mentioned

BETA
ubiquitination
transmission electron microscopy
light microscopy
Fluorescence Recovery After Photobleaching
neddylation
PCR
transfection
Fluorescence

Software Mentioned

Image Lab
ImageJ
Matlab
EasyFrap script
Metamorph

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