p53 target gene Rap2B regulates the cytoskeleton and inhibits cell spreading

J Cancer Res Clin Oncol. 2015 Oct;141(10):1791-8. doi: 10.1007/s00432-015-1948-8. Epub 2015 Mar 12.

Abstract

Purpose: Cell migration requires spatiotemporal integration of signals that target cytoskeletal. Previous studies have indicated that Rho GTPases are crucial regulators of actin dynamics. As homologs of Rho proteins, the role of Rap2B in the regulation of cytoskeleton and its cell signaling pathway remains unknown.

Methods: The cellular functions of Rap2B were monitored by Western blotting and immunofluorescence staining in order to characterize the protein level and the cell shape.

Results: Here, we show that expression of Rap2B was induced by nocodazole in a p53-dependent manner. However, Rap2B itself is not necessary for p53-dependent cell cycle arrest. We evidenced that over-expression of Rap2B may inhibit cell spreading by disrupting actin dynamics upon nocodazole treatment, but Rap2B (C180A) mutant does not. In contrast, knockdown of Rap2B promoted cell spreading.

Conclusions: Altogether, these results revealed that Rap2B plays a pivotal role in cytoskeleton reorganization and subsequently inhibits cell spreading, which could be responsible for cancer metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Cell Cycle Checkpoints / physiology
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cytoskeleton / metabolism*
  • Cytoskeleton / pathology*
  • Humans
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / metabolism*
  • rap GTP-Binding Proteins / metabolism*
  • rho GTP-Binding Proteins / metabolism

Substances

  • Actins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • RAP2B protein, human
  • rap GTP-Binding Proteins
  • rho GTP-Binding Proteins