Tumor suppressor p16INK4A inhibits cancer cell growth by downregulating eEF1A2 through a direct interaction

Mee Hyun Lee, Bu Young Choi, Yong Yeon Cho, Sung-Young Lee, Zunnan Huang, Joydeb Kumar Kundu, Myoung Ok Kim, Dong Joon Kim, Ann M. Bode, Young Joon Surh, Zigang Dong

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The tumor suppressor protein p16INK4a is a member of the INK4 family of cyclin-dependent kinase (Cdk) inhibitors, which are involved in the regulation of the eukaryotic cell cycle. However, the mechanisms underlying the anti-proliferative effects of p16INK4a have not been fully elucidated. Using yeast two-hybrid screening, we identified the eukaryotic elongation factor (eEF)1A2 as a novel interacting partner of p16INK4a. eEF1A2 is thought to function as an oncogene in cancers. The p16INK4a protein interacted with all but the D2 (250-327 aa) domain of eEF1A2. Ectopic expression of pp16INK4a decreased the expression of eEF1A2 and inhibited cancer cell growth. Furthermore, suppression of protein synthesis by expression of pp16INK4a ex vivo was verified by luciferase reporter activity. Microinjection of pp16INK4a mRNA into the cytoplasm of Xenopus embryos suppressed the luciferase mRNA translation, whereas the combination of pp16INK4a and morpholino-eEF1A2 resulted in a further reduction in translational activity. We conclude that the interaction of pp16INK4a with eEF1A2, and subsequent downregulation of the expression and function of eEF1A2 is a novel mechanism explaining the anti-proliferative effects of p16INK4a.

Original languageEnglish (US)
Pages (from-to)1744-1752
Number of pages9
JournalJournal of cell science
Volume126
Issue number8
DOIs
StatePublished - Apr 15 2013

Keywords

  • Anti-proliferative effects
  • Ovarian cancer
  • Translational activity
  • eEF1A2
  • p16

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    Lee, M. H., Choi, B. Y., Cho, Y. Y., Lee, S-Y., Huang, Z., Kundu, J. K., Kim, M. O., Kim, D. J., Bode, A. M., Surh, Y. J., & Dong, Z. (2013). Tumor suppressor p16INK4A inhibits cancer cell growth by downregulating eEF1A2 through a direct interaction. Journal of cell science, 126(8), 1744-1752. https://doi.org/10.1242/jcs.113613