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Homeodomain-interacting protein kinase-2 stabilizes p27(kip1) by its phosphorylation at serine 10 and contributes to

Giovanna Maria Pierantoni1, Francesco Esposito1, Mara Tornincasa1

  • 1Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli "Federico II," via Pansini 5, 80131 Naples, Italy and.

The Journal of Biological Chemistry
|July 1, 2011
PubMed

Insights

The serine/threonine kinase HIPK2 phosphorylates p27(kip1) at serine 10, impacting its stability and cell motility. This HIPK2-p27(kip1) interaction is crucial in tumor cells lacking wild-type p53.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • HIPK2 (Homeodomain-Interacting Protein Kinase 2) is a serine/threonine kinase regulating cell survival and proliferation.
  • HIPK2 acts as a coregulator for various factors involved in cellular processes.
  • The precise targets and functions of HIPK2 are still being elucidated.

Purpose of the Study:

  • To identify novel targets of HIPK2.
  • To investigate the functional significance of HIPK2-mediated phosphorylation of p27(kip1).
  • To explore the role of the HIPK2-p27(kip1) axis in cancer cell behavior.

Main Methods:

  • In vitro and in vivo kinase assays to determine HIPK2 phosphorylation sites on p27(kip1).
  • RNA interference (RNAi) to deplete HIPK2 in tumor cells.
  • Western blotting to assess p27(kip1) phosphorylation and stability.
  • Cell motility and proliferation assays.

Main Results:

  • HIPK2 directly phosphorylates p27(kip1) at serine 10, accounting for 80% of total p27(kip1) phosphorylation.
  • HIPK2-mediated phosphorylation at serine 10 is critical for p27(kip1) protein stability.
  • HIPK2 depletion reduces p27(kip1) phosphorylation and stability in tumor cells.
  • HIPK2 regulation of p27(kip1) influences cell motility, but not proliferation, in p53-wild-type-negative cells.

Conclusions:

  • HIPK2 is a novel kinase that phosphorylates and stabilizes p27(kip1) at serine 10.
  • This HIPK2-p27(kip1) interaction plays a role in cell motility, particularly in the context of p53 deficiency.
  • The findings reveal a new regulatory pathway with potential implications for cancer research.

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