PKM2介导沃伯格效应，在肿瘤发生中起着关键作用，但其在增生性皮肤疾病中的作用仍然不清楚。本研究调查了PKM2在银屑病性角质细胞中的功能。我们发现PKM2的表达及其核移位在银屑病患者的表皮中得到诱导，进而促进有氧糖酵解和细胞生长。此外，质谱联用免疫沉淀分析显示，PKM2能够与TRIM33相互作用，TRIM33是核中的一个E3泛素连接酶，这种相互作用对于PKM2的核滞留至关重要。由于TRIM33介导的泛素化作用，促进了PKM2的核蛋白激酶功能，从而导致STAT3的磷酸化。此外，抑制PKM2的核移位使TRIM33引发的糖酵解和角质细胞增殖受到抑制。综上所述，我们的实验表明泛素化调控了角质细胞中PKM2的核滞留。此外，我们的结果突出了银屑病患者角质细胞代谢重编程的新机制。© 2023 John Wiley & Sons A/S. 由John Wiley & Sons Ltd.发表。

PKM2 mediates the Warburg effects and is crucial for tumorigenesis, but its role in hyperplastic skin disorders remains elusive. In this study, we investigated the function of PKM2 in psoriatic keratinocytes. We found that PKM2 expression and its nuclear translocation were induced in the epidermis of psoriasis patients, contributing to aerobic glycolysis and cell growth. Moreover, mass spectrometry combined with immunoprecipitation analysis revealed that PKM2 could interact with TRIM33, an E3 ubiquitin ligase in the nucleus, and this interaction is critical for the nuclear retention of PKM2. As a result of TRIM33-mediated ubiquitination, PKM2 nuclear protein kinase function is promoted, thus leading to the phosphorylation of STAT3. In addition, blocking PKM2 nuclear translocation abrogated TRIM33-triggered glycolysis and cell proliferation in keratinocytes. Taken together, our experiments demonstrate that ubiquitination regulates the nuclear retention of PKM2 in keratinocytes. Moreover, our results highlight a novel mechanism accounting for the metabolic reprogramming of keratinocytes in psoriasis patients.© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.