Numb regulates stability and localization of the mitotic kinase PLK1 and is required for transit through mitosis

Travis L. Schmit, Minakshi Nihal, Mary Ndiaye, Vijayasaradhi Setaluri, Vladimir Spiegelman, Nihal Ahmad

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3864-3872
Number of pages9
JournalCancer Research
Volume72
Issue number15
DOIs
StatePublished - Aug 1 2012

Fingerprint

Tubulin
Mitosis
Phosphotransferases
Spindle Poles
Centrosome
Anaphase
Protein Stability
Aneuploidy
Threonine
Metaphase
Immunoprecipitation
Cell Division
Serine
Melanoma
Neoplasms
Cell Cycle
Stem Cells
Growth
polo-like kinase 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Schmit, Travis L. ; Nihal, Minakshi ; Ndiaye, Mary ; Setaluri, Vijayasaradhi ; Spiegelman, Vladimir ; Ahmad, Nihal. / Numb regulates stability and localization of the mitotic kinase PLK1 and is required for transit through mitosis. In: Cancer Research. 2012 ; Vol. 72, No. 15. pp. 3864-3872.
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Numb regulates stability and localization of the mitotic kinase PLK1 and is required for transit through mitosis. / Schmit, Travis L.; Nihal, Minakshi; Ndiaye, Mary; Setaluri, Vijayasaradhi; Spiegelman, Vladimir; Ahmad, Nihal.

In: Cancer Research, Vol. 72, No. 15, 01.08.2012, p. 3864-3872.

Research output: Contribution to journalArticle

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