PMID:23574721

Citation	Leonard, MK, Hill, NT, Bubulya, PA and Kadakia, MP (2013) The PTEN-Akt pathway impacts the integrity and composition of mitotic centrosomes. Cell Cycle 12:1406-15
Abstract	Loss of the tumor suppressor PTEN is observed in many human cancers that display increased chromosome instability and aneuploidy. The subcellular fractions of PTEN are associated with different functions that regulate cell growth, invasion and chromosome stability. In this study, we show a novel role for PTEN in regulating mitotic centrosomes. PTEN localization at mitotic centrosomes peaks between prophase and metaphase, paralleling the centrosomal localization of PLK-1 and γ-tubulin and coinciding with the time frame of centrosome maturation. In primary keratinocytes, knockdown of PTEN increased whole-cell levels of γ-tubulin and PLK-1 in an Akt-dependent manner and had little effect on recruitment of either protein to mitotic centrosomes. Conversely, knockdown of PTEN reduced centrosomal levels of pericentrin in an Akt-independent manner. Inhibition of Akt activation with MK2206 reduced the whole-cell and centrosome levels of PLK-1 and γ-tubulin and also prevented the recruitment of PTEN to mitotic centrosomes. This reduction in centrosome-associated proteins upon inhibition of Akt activity may contribute to the increase in defects in centrosome number and separation observed in metaphase cells. Concomitant PTEN knockdown and Akt inhibition reduced the frequency of metaphase cells with centrosome defects when compared with MK2206 treatment alone, indicating that both PTEN and pAkt are required to properly regulate centrosome composition during mitosis. The findings presented in this study demonstrate a novel role for PTEN and Akt in controlling centrosome composition and integrity during mitosis and provide insight into how PTEN functions as a multifaceted tumor suppressor.
Links	PubMed PMC3674068 Online version:10.4161/cc.24516
Keywords	Antigens/metabolism; Cell Cycle Proteins/metabolism; Centrosome/metabolism; Enzyme Activation; Humans; Infant, Newborn; Keratinocytes/cytology; Keratinocytes/enzymology; Mitosis; PTEN Phosphohydrolase/metabolism; Protein Transport; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-akt/metabolism; Signal Transduction; Tubulin/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PTEN		GO:0005813: centrosome	ECO:0000314:		C		Figure 1	complete CACAO 12098

References

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