The centrosomal FOP protein is required for cell cycle progression and survival

Abstract

Cell Cycle 1217FOP is a centrosomal protein originally discovered as a fusion partner of FGFR1 in patients with a rare stem cell myeloproliferative disorder. In DT40 chicken lymphocytes, we show that the normal FOP protein localizes at the centrosome throughout the cell cycle and preferentially accumulates at the distal end of the mother centriole. We used homologous recombination in DT40 cells to generate an inducible null mutant for FOP. Loss of FOP induces apoptosis in the G 1 phase of the cell cycle with accumulation of a 32 kDa P53 tumor suppressor isoform and NOXA and FAS transcripts. However, centrosome integrity and microtubule organization are conserved without FOP and mitotic division and cytokinesis are as efficient as in control cells. Our results suggest that FOP is involved in G 1 to S signaling and thus in proliferation/death fate. Several reports show that centrosome alteration can lead to an arrest in G 1 and, possibly, to senescence in a fraction of cells. The phenotype we observed is more severe in FOP null cells. This could be dependent on the cell context or on the efficiency of a knock out that allows the complete disappearance of the target protein and prevents any de novo synthesis. This is an important observation in regard to the current discussion of what consequence centrosome perturbation could have on a cell and shows that a centrosomal protein can be necessary for cell cycle progression and survival.

A protein phosphatase 2A complex spatially controls plant cell division

“…This ranges from whole protein similarity between PP2A subunits (including FASS), to domains conserved between TON1 and FOP, and to conserved motifs between TRM proteins and CAP350 (refs 11,16,17 51 ). However, and although animal counterparts of the three core TTP components were recently co-purified in human cells 52 , the function of the TTP network as a whole has not been formally studied in any system apart from plants.…”

Control of ciliogenesis by FOR20, a novel centrosome and pericentriolar satellite protein

“…This protein, named FOR20, is related to FOP (Acquaviva et al, 2009;Popovici et al, 1999), and more distantly to OFD1 (Ferrante et al, 2006;Romio et al, 2004). In vivo, deficiencies in OFD1 and FOP promote ciliopathic syndromes (Ferrante et al, 2001;Ferrante et al, 2006) (C.A.…”

“…We used the tBLASTn program to find proteins with sequence similarity to the centrosomal FOP (FGFR1 Oncogene Partner) protein (Acquaviva et al, 2009;Popovici et al, 1999) and identified a small conserved putative protein showing low but significant similarity with FOP N-terminal region in humans. This putative new protein, C16orf63/FLJ31153 in GenBank, was named FOR20 (FOP-related protein of 20 kDa) (Fig.…”

“…The cells were washed three times with PBS containing 0.1% BSA and 0.1% Tween 20, and were incubated with goat anti-rat antibody conjugated to 6 nm colloidal gold (1/40; Jackson Laboratories) and goat anti-rabbit antibody conjugated to 18 nm colloidal gold (1/40; Jackson Laboratories) for 1 hour. For electron microscopy cells were fixed with 2.5% glutaraldehyde and processed for dehydration and embedding, as described previously (Acquaviva et al, 2009). …”

The Pathogenesis of Vitiligo

“…When this gene is overexpressed, it makes cells more vulnerable to oxidative stress (Thompson et al, 2009), an important mechanism for melanocyte destruction. The two genes are FGFR10P, which encodes a fibroblast growth factor receptor and can play a role in cell cycle progression in some disorders (Acquaviva et al, 2009), and the chemokine receptor 6 gene (CCR6) (Quan et al, 2010). Another HLA-oriented study by de Castro et al (2010) examined the gene encoding the discoidin domain receptor 1 (DDR1).…”