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The functional repertoire of survivin's tails

Sally P Wheatley1

  • 1a From the School of Life Sciences ; University of Nottingham; Queen's Medical Centre ; Nottingham , UK.

Cell Cycle (Georgetown, Tex.)
|January 22, 2015
PubMed

Insights

The C-terminus of survivin is essential for cell division, while the N-terminus is not required for apoptosis or mitosis but protects against irradiation-induced cell death.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Survivin is a protein involved in inhibiting cell death and essential for mitosis.
  • Its expression correlates with tumor resistance to cancer treatments, making it a potential therapeutic target.
  • The precise molecular functions of survivin's termini are not fully understood.

Purpose of the Study:

  • To investigate whether the extreme C- and NH2 termini of survivin are necessary for its cytoprotective and mitotic functions.
  • To elucidate the specific roles of survivin's termini in apoptosis, mitosis, and response to irradiation.

Main Methods:

  • Truncated survivin variants (survivin1-120 and survivin11-142) were created and expressed in cells.
  • Cells expressing these variants were challenged with TRAIL-mediated apoptosis and irradiation.
  • The localization and function of survivin variants during mitosis were analyzed.

Main Results:

  • Both survivin1-120 and survivin11-142 protected cells against TRAIL-mediated apoptosis.
  • Survivin11-142 did not provide a survival advantage against irradiation.
  • Truncation of the C-terminus (survivin1-120) impaired midzone microtubule localization during anaphase.
  • Removal of the N-terminus (survivin11-142) did not affect mitosis.

Conclusions:

  • The C-terminus of survivin is crucial for proper cell division.
  • The N-terminus is dispensable for apoptosis and mitosis but is required for protection against irradiation.
  • These findings highlight distinct roles for survivin's termini in cellular processes and stress responses.
Keywords:
CPC, chromosomal passenger complexCPP, chromosomal passenger proteinIAP, inhibitor of apoptosisIR, irradiationNES, nuclear exportation signalSVN, survivinTRAIL, Tumor-necrosis factor Responsive Apoptosis Inducing LigandWT, wild typeapoptosiscancerirradiationmitosissurvivin

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