The steroid hormone 20-hydroxyecdysone inhibits RAPTOR expression by repressing Hox gene transcription to induce

Tian-Wen Liu1, Can Tian1, Yan-Xue Li1

  • 1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, China.

PubMed

Insights

Homeobox (HOX) proteins promote Raptor transcription, enhancing cell growth. 20-Hydroxecdysone (20E) represses HOX, leading to autophagy and reduced cell proliferation during insect metamorphosis.

Area of Science:

  • Molecular and developmental biology
  • Insect molecular biology
  • Cellular regulation

Background:

  • Regulatory-associated protein of TOR (RAPTOR) is crucial for TOR complex 1, impacting cell growth and autophagy.
  • While post-translational modifications of RAPTOR are studied, its transcriptional regulation remains largely unknown.
  • Understanding Raptor's transcriptional control is vital for insect development and physiology.

Purpose of the Study:

  • To elucidate the transcriptional regulatory mechanism of Raptor in the cotton bollworm (Helicoverpa armigera).
  • To investigate the roles of 20-Hydroxecdysone (20E) and Homeobox (HOX) proteins in regulating Raptor expression.
  • To determine the impact of Raptor regulation on insect development, autophagy, and cell proliferation.

Main Methods:

  • Analysis of Raptor expression profiles across different tissues and developmental stages (larva to pupa).
  • Gene knockdown experiments to assess the functional consequences of Raptor disruption.
  • Investigation of the regulatory interactions between 20E, HOX proteins, and the Raptor promoter using molecular techniques.

Main Results:

  • Raptor exhibits stage- and tissue-specific expression, with high levels during larval feeding and low levels during metamorphosis.
  • Raptor knockdown at the feeding stage leads to smaller pupae and increased autophagy; knockdown during metamorphosis impairs development.
  • 20E represses Raptor transcription, while HOX proteins promote it by binding to the Raptor promoter. 20E also represses HOX transcription.

Conclusions:

  • HOX proteins act as positive transcriptional regulators of Raptor, promoting cell proliferation and inhibiting autophagy.
  • 20E, through its nuclear receptor EcR, represses HOX gene transcription, consequently downregulating Raptor expression.
  • This regulatory axis involving HOX and 20E controls the balance between cell proliferation and autophagy during insect metamorphosis.

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