Stathmin/Op18 depletion induces genomic instability and leads to premature senescence in human normal fibroblasts

Deepmala Shrestha, Namil Kim, Kiwon Song

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Stathmin/oncoprotein18 regulates microtubule dynamics and participates in mitotic entry and exit. We isolated stathmin as a physically interacting partner of KIFC1, a minus-end-directed kinesin functioning in bipolar spindle formation and maintenance. We found that stathmin depletion leads to multipolar spindle formation in IMR-90 normal human fibroblasts. Stathmin-depleted IMR-90 cells showed early mitotic delay but managed to undergo chromosome segregation by forming multiple poles or pseudo-bipoles. Consistent with these observations, lagging chromosomes, and micronuclei were elevated in stathmin-depleted IMR-90 cells, demonstrating that stathmin is essential for maintaining genomic stability during mitosis in human cells. Genomic instability induced by stathmin depletion led to premature senescence without any indication of cell death in normal IMR-90 cells. Double knock-down of both stathmin and p53 also did not induce cell death in IMR-90 cells, while the stathmin knock-down triggered apoptosis in p53-proficient human lung adenocarcinoma cells. Our results suggest that stathmin is essential in bipolar spindle formation to maintain genomic stability during mitosis, and the depletion of stathmin prevents the initiation of chromosome instability by inducing senescence in human normal fibroblasts.

Original languageEnglish
Pages (from-to)2381-2395
Number of pages15
JournalJournal of Cellular Biochemistry
Volume119
Issue number2
DOIs
Publication statusPublished - 2018 Feb

Bibliographical note

Funding Information:
The authors would like to thank Dr. Royoma Ohi (Vanderbilt University) for generously providing the anti-centrin antibody and for helpful comments regarding this manuscript. This work was supported by the National Research Foundation of Korea (NRF) funded to K. Song (No. NRF-2017R1A2B4009785). D. Shrestha was supported in part by the BK21 and BK21 PLUS programs.

Funding Information:
National Research Foundation (NRF) of Korea, Grant number: NRF- 2017R1A2B4009785

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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