Identification of subcellular targeting sequences of Cten reveals its role in cell proliferation

Shiao Ya Hong, Yi Ping Shih, Abigail Lo, Su Hao Lo

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Spatial and temporal subcellular localization plays critical roles in regulating protein function. Cten (C-terminal tensin like) is a member of the tensin family. Cten recruits signaling molecules, such as DLC1, to focal adhesions, modulates homeostasis of receptor tyrosine kinases, including EGFR and c-Met, and promotes cell migration. These functions are likely controlled by Cten localization at focal adhesions and/or in the cytoplasm. In addition, Cten has been detected in the nucleus by which mechanism is unknown. To this end, we have examined the distribution of Cten in various cell lines, determined primary sequence requirements for its nuclear and focal adhesion localizations, and analyzed potential roles of nuclear Cten. Our results show that a proportion of Cten translocates to nuclei in cancer cell lines and that nuclear exporting of Cten is a CRM1-dependent process. A nuclear localization sequence and a nuclear export sequence are identified within Cten. In addition, like other tensins, Cten contains two independent focal adhesion binding sites. Although further expression of recombinant Cten showed no effect on cancer cell proliferation, silencing of Cten significantly reduced cell growth. Furthermore, expression of Cten mutants either with defective nuclear export sequence or tagged with SV40 nuclear localization sequence promoted cell growth. These results suggest that nuclear Cten contributes to cancer cell proliferation. Our findings identify a molecular mechanism for regulating Cten protein trafficking in mammalian cells and provide new insights into the dynamics of focal adhesion complexes in health and disease.

Original languageEnglish (US)
JournalBiochimica et Biophysica Acta - Molecular Cell Research
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

Cell Proliferation
Focal Adhesions
Tensins
Cell Nucleus Active Transport
Cell Line
Neoplasms
Receptor Protein-Tyrosine Kinases
Protein Transport
Growth
Cell Movement
Cytoplasm
Homeostasis
Binding Sites

Keywords

  • Cten
  • Focal adhesion
  • Nucleus
  • Tensin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Identification of subcellular targeting sequences of Cten reveals its role in cell proliferation. / Hong, Shiao Ya; Shih, Yi Ping; Lo, Abigail; Lo, Su Hao.

In: Biochimica et Biophysica Acta - Molecular Cell Research, 01.01.2018.

Research output: Contribution to journalArticle

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