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Updated: Jun 6, 2025

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
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Published on: October 28, 2014

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p21Waf1/Cip1 Is a Novel Downstream Target of 40S Ribosomal S6 Kinase 2

Alakananda Basu1, Zhenyu Xuan2

  • 1Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.

Cancers
|November 27, 2024
PubMed

Insights

Ribosomal S6 kinase 2 (S6K2) promotes breast cancer cell survival by downregulating p21 and Mcl-1. Silencing S6K2 sensitizes cells to doxorubicin, offering potential therapeutic strategies.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Ribosomal S6 kinase 2 (S6K2) is a homolog of S6K1, downstream of mTORC1.
  • The downstream effectors and functions of S6K2 in breast cancer are not well understood.

Purpose of the Study:

  • To investigate the role of S6K2 in breast cancer cell survival.
  • To identify novel downstream targets of S6K2 using transcriptome profiling.

Main Methods:

  • RNA-sequencing (RNA-Seq) for target identification.
  • siRNA and plasmid transfections for gene manipulation.
  • Western blot for protein analysis.
  • Doxorubicin treatment to assess apoptosis.

Main Results:

  • S6K2 silencing, not S6K1, decreased p21 levels in breast cancer cells.
  • Akt1 and Akt2 influenced p21 levels differently across cell lines.
  • S6K2 knockdown increased JUN mRNA, and cJun knockdown enhanced p21.
  • S6K2 or p21 silencing sensitized cells to doxorubicin via JNK-mediated Mcl-1 downregulation.

Conclusions:

  • S6K2 knockdown enhances doxorubicin-induced apoptosis.
  • This effect is mediated by the downregulation of p21 and Mcl-1.
  • The Akt and JNK signaling pathways are involved in S6K2's regulation of apoptosis.
Keywords:
Akt1Akt2JNKS6K1S6K2/RPS6KB2apoptosisbreast cancercJun/JUNchemoresistancep21/CDKN1A

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