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Protein kinase C-dependent phosphorylation regulates the cell cycle-inhibitory function of the p73 carboxy terminus

Ulrika Nyman1, Pinelopi Vlachos, Anna Cascante

  • 1Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.

Molecular and Cellular Biology
|January 23, 2009
PubMed

Insights

The transcription factor p73 regulates cell cycle arrest and apoptosis through distinct domains. A novel carboxy-terminal domain and its phosphorylation control cell cycle progression, offering new insights into p73 functions.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The transcription factor p73, part of the p53 protein family, plays a role in cell cycle regulation and apoptosis.
  • Mechanisms governing p73's distinct functions in these processes are not fully understood.

Purpose of the Study:

  • To elucidate the regulatory mechanisms controlling p73's distinct roles in cell cycle arrest and apoptosis.
  • To identify and characterize novel functional domains and regulatory modifications of p73.

Main Methods:

  • Functional analysis of p73 domains in cell cycle arrest and apoptosis induction.
  • Characterization of a novel carboxy-terminal transactivation domain (residues 381-399).
  • Investigation of posttranslational modifications, specifically protein kinase C-dependent phosphorylation at Serine 388.

Main Results:

  • p73 induces cell cycle arrest independently of its amino-terminal transactivation domain, which is essential for apoptosis.
  • A second transactivation domain in the p73 carboxy terminus (residues 381-399) preferentially regulates cell cycle progression genes.
  • This carboxy-terminal domain's activity is cell cycle-regulated and modulated by PKC-dependent phosphorylation at Ser388.

Conclusions:

  • The amino-terminal domain of p73 is critical for apoptosis, while the carboxy-terminal domain regulates cell cycle arrest.
  • Phosphorylation at Ser388 within the carboxy-terminal domain is a key posttranslational modification that guides p73's selective induction of cell cycle arrest.

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