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Cell cycle arrest and apoptosis by expression of a novel TPIP (TPIP-C2) cDNA encoding a C2-domain in HEK-293 cells

Rasmi Rekha Mishra1, Jitendra Kumar Chaudhary, Pramod C Rath

  • 1Molecular Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

Molecular Biology Reports
|February 8, 2012
PubMed

Insights

A novel TPIP-C2 protein fragment, similar to PTEN, inhibits cell proliferation and induces apoptosis. This C2-domain may act as a dominant negative effector, offering potential in cancer therapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • The PTEN (Phosphatase and TENsin homologue deleted on chromosome 10) tumor suppressor regulates cell functions via its C2-domain.
  • The role of isolated C2-domain proteins in cell proliferation and apoptosis remains largely uninvestigated.

Purpose of the Study:

  • To analyze the sequence and function of a novel human TPIP (TPTE and PTEN homologous Inositol lipid Phosphatase) C2-domain (TPIP-C2) cDNA.
  • To investigate the role of TPIP-C2 in regulating cell proliferation and apoptosis.

Main Methods:

  • In silico analysis and homology modeling of TPIP-C2.
  • Overexpression of TPIP-C2 cDNA in human embryonic kidney (HEK-293) cells.
  • Cell cycle analysis and apoptosis assays (caspase 3, PARP).

Main Results:

  • TPIP-C2 shares structural similarities with PTEN's C2-domain but has unique disordered regions.
  • Overexpression of TPIP-C2 induced S-phase cell cycle arrest, inhibited proliferation, and triggered apoptosis in HEK-293 cells.
  • Apoptosis was dependent on activated caspase 3 and PARP.

Conclusions:

  • The TPIP-C2 C2-domain may function as a dominant negative effector, potentially arresting cell proliferation signaling complexes.
  • Isolated TPIP-C2 domain-like proteins could play a significant role in mammalian cell proliferation and apoptosis regulation.
  • TPIP-C2 cDNA presents a potential therapeutic strategy for inducing cell cycle inhibition and apoptosis in human cancers.

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