Ornithine decarboxylase regulates the activity and localization of rhoA via polyamination

Journal Article · Wed Apr 01 04:00:00 EDT 2009 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2009.01.029· OSTI ID:21176193

Maekitie, Laura T; Kanerva, Kristiina ^[1]; Andersson, Leif C ^[1]

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1. Department of Pathology, Haartman Institute, P.O. Box 21, 00014 University of Helsinki (Finland)

Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis. Polyamines and ODC are connected to cell proliferation and transformation. Resting cells display a low ODC activity while normal, proliferating cells display fluctuations in ODC activity that coincide with changes in the actin cytoskeleton during the cell cycle. Cancerous cells display constitutively elevated ODC activity. Overexpression of ODC in NIH 3T3 fibroblasts induces a transformed phenotype. The cytoskeletal rearrangements during cytokinesis and cell transformation are intimately coupled to the ODC activity but the molecular mechanisms have remained elusive. In this study we investigated how ODC and polyamines influence the organization of the cytoskeleton. Given that the small G-proteins of the rho family are key modulators of the actin cytoskeleton, we investigated the molecular interactions of rhoA with ODC and polyamines. Our results show that transglutaminase-catalyzed polyamination of rhoA regulates its activity. The polyamination status of rhoA crucially influences the progress of the cell cycle as well as the rate of transformation of rat fibroblasts infected with temperature-sensitive v-src. We also show that ODC influences the intracellular distribution of rhoA. These findings provide novel insights into the mechanisms by which ODC and polyamines regulate the dynamics of the cytoskeleton during cell proliferation and transformation.

• OSTI ID: 21176193
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 6 Vol. 315; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
CELL CYCLE
CELL PROLIFERATION
CELL TRANSFORMATIONS
DECARBOXYLASES
FIBROBLASTS
GTP-ASES
MICROTUBULES
ORNITHINE
PHENOTYPE
RATS
TRANSFORMATIONS