TY - JOUR
T1 - Numb regulates stability and localization of the mitotic kinase PLK1 and is required for transit through mitosis
AU - Schmit, Travis L.
AU - Nihal, Minakshi
AU - Ndiaye, Mary
AU - Setaluri, Vijayasaradhi
AU - Spiegelman, Vladimir S.
AU - Ahmad, Nihal
PY - 2012/8/1
Y1 - 2012/8/1
N2 - Numb functions in progenitor cell fate determination and early development, but it is also expressed in postdevelopmental tissues and cancers where its role is unclear. In this study, we report that a targeted knockdown of Numb expression causes a G2-M arrest and reduced cell growth in human melanoma cells. Co-immunoprecipitation and colocalization studies showed that Numb interacts with the serine/threonine polo-like kinase Plk1 and Numb cycles in a cell-cycle -dependent fashion along with this mitotic regulator. Interestingly, Numb expression was required for Plk1 protein stability and localization to the spindle poles during mitosis. Reduction in Numb expression resulted in mislocalization of Plk1 at both metaphase and anaphase, leading to disorganized γ-tubulin recruitment in centrosomes. Together, our findings present a novel function for Numb during symmetric cell division. We suggest that dysregulation of Numb expression results in mislocalized Plk1 and poor centrosomal γ-tubulin recruitment, potentially contributing to mitotic errors, aneuploidy, and cancer development.
AB - Numb functions in progenitor cell fate determination and early development, but it is also expressed in postdevelopmental tissues and cancers where its role is unclear. In this study, we report that a targeted knockdown of Numb expression causes a G2-M arrest and reduced cell growth in human melanoma cells. Co-immunoprecipitation and colocalization studies showed that Numb interacts with the serine/threonine polo-like kinase Plk1 and Numb cycles in a cell-cycle -dependent fashion along with this mitotic regulator. Interestingly, Numb expression was required for Plk1 protein stability and localization to the spindle poles during mitosis. Reduction in Numb expression resulted in mislocalization of Plk1 at both metaphase and anaphase, leading to disorganized γ-tubulin recruitment in centrosomes. Together, our findings present a novel function for Numb during symmetric cell division. We suggest that dysregulation of Numb expression results in mislocalized Plk1 and poor centrosomal γ-tubulin recruitment, potentially contributing to mitotic errors, aneuploidy, and cancer development.
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U2 - 10.1158/0008-5472.CAN-12-0714
DO - 10.1158/0008-5472.CAN-12-0714
M3 - Article
C2 - 22593191
AN - SCOPUS:84864836812
SN - 0008-5472
VL - 72
SP - 3864
EP - 3872
JO - Cancer Research
JF - Cancer Research
IS - 15
ER -