GFPT1 regulates AMPK activity through enhanced O-GlcNAcylation

• 발행기관: 한국구조생물학회
• 저자명: Chibuzo Sampson Shaojun Pei Jing Lv Di Chen Yegang Ma Tian Xia Hai-long Piao
• 간행물 정보: 『Biodesign』Vol 13, No 2, Jun, 22~33쪽, 전체 12쪽
• 주제분류: 자연과학 > 생물학
• 파일형태: PDF
• 발행일자: 2025.06.30

국문 초록

Metabolic reprogramming is increasingly recognized as a cause of diverse human diseases. This study investigates the relationship between two key metabolic regulators, glutamine-fructose-6-phosphate transaminase 1 (GFPT1) and AMP-activated protein kinase (AMPK), within the context of the hexosamine biosynthesis pathway (HBP). While AMPK has been shown to regulate GFPT1 activity under glucose-restricted conditions, the reciprocal influence of GFPT1 on AMPK activity remains poorly understood. Here, we demonstrate that AMPK activity was significantly attenuated in cells lacking GFPT1 or treated with pharmacological GFPT1 inhibitor. Remarkably, glucosamine, a downstream metabolite of the HBP that promotes glycosylation, restored AMPK activity in GFPT1-deficient cells. Moreover, GFPT1 was found to be indispensable for cancer cell proliferation especially under glucose-limited conditions. These findings highlight GFPT1 as a pivotal regulator of AMPK activity through HBP-mediated glycosylation. This study identifies GFPT1 as a critical driver of metabolic adaptation in cancer and a promising therapeutic target for cancer treatment.

목차

INTRODUCTION

RESULTS

DISCUSSION

MATERIALS AND METHODS

SUPPLEMENTARY MATERIALS

ACKNOWLEDGEMENTS

AUTHOR CONTRIBUTIONS

DATA AVAILABLE STATEMENT

CONFLICT OF INTEREST

REFERENCES

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