Work

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

Year: 2024

Type: article

Abstract: Regulatory-associated protein of TOR (RAPTOR) is a key component of TOR complex 1, which determines the lysosomal location and substrate recruitment of TOR complex 1 to promote cell growth and prevent autophagy. Many studies in recent decades have focused on the post-translational modification of RAPTOR; however, little is known about the transcriptional regulatory mechanism of Raptor. Using the lepidopteran insect cotton bollworm (Helicoverpa armigera) as model, we reveal the transcriptional regulatory mechanism of Raptor. RAPTOR has different expression profiles in tissues during development from larva to late pupa, with high expression levels at larval feeding stages but low expression levels during metamorphic stages in the epidermis, midgut, and fat body. RAPTOR is localized in the larval midgut at the feeding stage but is localized in the imaginal midgut at metamorphic stages. The knockdown of Raptor at the feeding stage results in the production of small pupae, early autophagy of the midgut and fat body, and decreased cell proliferation. However, Raptor knockdown at metamorphic stage represses the development of the epidermis, adult fat body, and brain. 20-Hydroxecdysone (20E) represses Raptor transcription. Homeobox (HOX) proteins promote Raptor transcription by binding to its promoter. Overexpression of HOX proteins represses autophagy-related gene expression and autophagy but increases cell proliferation. 20E represses Hox genes transcription via its nuclear receptor EcR binding to its promoters. Together, these findings suggest that HOX proteins are positive regulators that upregulate Raptor transcription. 20E represses Hox gene transcription, thus repressing Raptor expression, resulting in autophagy and repressing cell proliferation during metamorphosis.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2024.108093

Authors: Tian-Wen Liu, Can Tian, Yan-Xue Li, Jin-Xing Wang, Xiao-Fan Zhao

Institution: Shandong University

Language: English

Topic: Autophagy in Disease and Therapy

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

Open Access status: gold

Estimated APC paid: $2,800

Funders: Shandong University, National Natural Science Foundation of China