Sgt1, a co-chaperone of Hsp90 stabilizes Polo and is required for centrosome organization

Abstract

Sgt1 was described previously in yeast and humans to be a Hsp90 co‐chaperone and required for kinetochore assembly. We have identified a mutant allele of Sgt1 in Drosophila and characterized its function. Mutations in sgt1 do not affect overall kinetochore assembly or spindle assembly checkpoint. sgt1 mutant cells enter less frequently into mitosis and arrest in a prometaphase‐like state. Mutations in sgt1 severely compromise the organization and function of the mitotic apparatus. In these cells, centrioles replicate but centrosomes fail to mature, and pericentriolar material components do not localize normally resulting in highly abnormal spindles. Interestingly, a similar phenotype was described previously in Hsp90 mutant cells and correlated with a decrease in Polo protein levels. In sgt1 mutant neuroblasts, we also observe a decrease in overall levels of Polo. Overexpression of the kinase results in a substantial rescue of the centrosome defects; most cells form normal bipolar spindles and progress through mitosis normally. Taken together, these findings suggest that Sgt1 is involved in the stabilization of Polo allowing normal centrosome maturation, entry and progression though mitosis.

Scrib regulates HGF-mediated epithelial morphogenesis and is stabilized by Sgt1-HSP90

“…Immunofluorescent staining of Sgt1 in subconfluent MDCK cells grown on a 2D surface revealed a broad cytoplasmic distribution as well as staining at the midbody similar to what has been previously described (not shown) (Martins et al, 2009;Steensgaard et al, 2004). Despite this broad distribution, Sgt1 could clearly be seen enriched along a filamentous network ( Fig.…”

Dynamic Nucleotide-dependent Interactions of Cysteine- and Histidine-rich Domain (CHORD)-containing Hsp90 Cochaperones Chp-1 and Melusin with Cochaperones PP5 and Sgt1

“…On the other hand, Chp-1, also known as morgana, has been shown to inhibit Rho kinase II, preventing centrosome amplification (23). Like Chp-1, Sgt1 in Drosophila participates in centrosome maturation through stabilizing Polo, the upstream kinase of Rho kinase (24,25). In addition, the Hsp90-Sgt1 chaperone complex is engaged in kinetochore formation in both yeast and mammals (26,27).…”

MLL5 Maintains Genomic Integrity by Regulating the Stability of the Chromosomal Passenger Complex via a Functional Interaction with Borealin

“…The CPC component Survivin has been shown to interact with HSP90 and disruption of the interaction destabilizes Survivin, results in mitotic defects and mitochondrialdependent apoptosis (Fortugno et al, 2003). Similarly, Pololike kinase is also under the HSP90 molecular chaperone regulation, in which SGT1 serves as a co-chaperone of HSP90 in stabilizing the kinase, allowing normal centrosome maturation, entry and progression through mitosis (de Cárcer et al, 2001;Martins et al, 2009). Mutations in SGT1 severely compromise the organization and function of the mitotic apparatus (Martins et al, 2009).…”

“…Similarly, Pololike kinase is also under the HSP90 molecular chaperone regulation, in which SGT1 serves as a co-chaperone of HSP90 in stabilizing the kinase, allowing normal centrosome maturation, entry and progression through mitosis (de Cárcer et al, 2001;Martins et al, 2009). Mutations in SGT1 severely compromise the organization and function of the mitotic apparatus (Martins et al, 2009). These studies further prompt us to speculate that the role of MLL5 in Borealin stability regulation might be like a molecular co-chaperone, where it cooperates with the chaperone proteins to maintain the stability of the CPC, and facilitates the proper mitotic progression.…”