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Updated: Jun 6, 2026

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
10:56

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Published on: May 17, 2014

The nuts-and-bolts of ribosomal protein s6 kinase 1 regulation: A shared responsibility for mTOR complexes 1 and 2

Sheikh Tahir Majeed1, Rabiya Majeed1,2, Khurshid I Andrabi1

  • 1Growth Factor Signaling laboratory, Department of Biotechnology, University of Kashmir, Srinagar, India.

The FEBS Journal
|June 5, 2026
PubMed

Insights

Ribosomal protein S6 kinase 1 (S6K1) activation is a two-step process involving mTORC1 and mTORC2 complexes. This revised understanding offers new therapeutic strategies for cancer and metabolic diseases.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Ribosomal protein S6 kinase 1 (S6K1) is a key regulator of cell growth, metabolism, and a central component of the mTOR signaling pathway.
  • Dysregulation of S6K1 is implicated in cancer and metabolic diseases, making it a significant therapeutic target.
  • A clear understanding of S6K1 activation mechanisms is crucial for developing effective treatments.

Purpose of the Study:

  • To provide a comprehensive review of S6K1 biology, focusing on its activation mechanisms.
  • To synthesize current knowledge on S6K1 structure, modifications, and regulation by noncoding RNAs.
  • To highlight the shift from canonical to non-canonical models of S6K1 activation.

Main Methods:

  • Literature review and synthesis of existing research on S6K1.
  • Analysis of structural, chemical modification, and regulatory data.
  • Integration of canonical and non-canonical activation models.

Main Results:

  • S6K1 activation is proposed to be a two-step mechanism involving both mTORC1 and mTORC2.
  • mTORC1 acts as a 'primer' by relieving internal constraints on S6K1.
  • mTORC2 completes the activation process, reconciling previous models and addressing drug sensitivity.

Conclusions:

  • A modern framework for S6K1 biology is established, integrating canonical and non-canonical activation pathways.
  • The proposed two-step activation mechanism provides new insights into S6K1 regulation.
  • This understanding opens avenues for precise therapeutic interventions targeting S6K1 in diseases.
Keywords:
eIF4EmTORC1mTORC2phosphorylationrapamycinribosomal protein S6 Kinase 1signal transduction

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