PIK-24 Inhibits RSV-Induced Syncytium Formation via Direct Interaction with the p85α Subunit of PI3K

Chen, Lifeng; Xu, Weibin; Xiong, Si; Cai, Jun-Xing; Zhang, Jingjing; Li, Man‐Mei; Zhang, Hong; Liu, Zhong

doi:10.1128/jvi.01453-22

Cited by 3 publications

(2 citation statements)

References 59 publications

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“…Recent research has uncovered isoform‐specific regulation in class IA and IB PI3Ks 10 with regulatory subunits playing a crucial role. For example, p85α inhibits p110α activity, while p85β enhances it 11 . Furthermore, the p110α subunit interacts with other proteins to regulate cellular processes beyond PI3K signaling 12 .…”

Section: Introductionmentioning

confidence: 99%

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PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A

Lin

Wang

et al. 2023

Cancer Medicine

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Section: Introductionmentioning

confidence: 99%

“…For example, p85α inhibits p110α activity, while p85β enhances it. 11 Furthermore, the p110α subunit interacts with other proteins to regulate cellular processes beyond PI3K signaling. 12 These advancements provide valuable insights into the regulation of the pathway and its impact on cell biology and disease.…”

Section: Introductionmentioning

confidence: 99%

PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A

Lin

Wang

et al. 2023

Cancer Medicine

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Natural killer cell migration in HIV-infected individuals is inhibited by impairment of HIF-1α-mediated glycolysis

Yu,

Zhou,

Lei

et al. 2024

Preprint

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Natural killer (NK) cells serve as the first line of defense of the immune system and play a crucial role in fighting against HIV infection. The effective function of NK cells is closely related to their migration ability, but the status of NK cell migration in HIV-infected individuals and the regulation mechanism for NK cell migration remains unknown. Here, we found that NK cell migration was significantly impaired in HIV-infected individuals, lower in immune non-responders (INRs) compared with immune responders (IRs), and positively correlated with CD4+T cell counts. Further investigations showed that the decreased NK cell migration in HIV infection was caused by the impairment of glycolysis. Mechanistically, we found that NK cell migration was regulated by HIF-1α pathway, and inhibitory receptor TIGIT restrained HIF-1α expression by inhibiting PI3K/AKT/mTORC1 or ERK signaling pathway, consequently weakening the glycolysis of NK cells in HIV-infected individuals, and ultimately leading to down-regulation of migration. Collectively, we uncovered a mechanism of reduced NK cell migration in HIV infection and provided a new insight for immunotherapy in HIV infection.In BriefThe effective function of NK cells is closely related to its migration ability. The authors show that impaired NK cell migration in HIV-infected individuals is caused by TIGIT inhibiting HIF-1α-mediated glycolysis via PI3K/AKT/mTORC1 or ERK pathway.

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PI3K p85α/HIF-1α accelerates the development of pulmonary arterial hypertension by regulating fatty acid uptake and mitophagy

Chen,

Qin,

Song

et al. 2024

Mol Med

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Background Pulmonary arterial hypertension (PAH) is characterized by lipid accumulation and mitochondrial dysfunction. This study was designed to investigate the effects of hypoxia-inducible factor-1α (HIF-1α) on fatty acid uptake and mitophagy in PAH. Methods Peripheral blood samples were obtained from PAH patients. Human pulmonary arterial smooth muscle cells and rat cardiac myoblasts H9c2 were subjected to hypoxia treatment. Male Sprague–Dawley rats were treated with monocrotaline (MCT). Right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), pulmonary artery remodeling, and lipid accumulation were measured. Cell proliferation and ROS accumulation were assessed. Mitochondrial damage and autophagosome formation were observed. Co-immunoprecipitation was performed to verify the interaction between HIF-1α and CD36/PI3K p85α. Results HIF-1α, CD36, Parkin, and PINK1 were upregulated in PAH samples. HIF-1α knockdown or PI3K p85α knockdown restricted the expression of HIF-1α, PI3K p85α, Parkin, PINK1, and CD36, inhibited hPASMC proliferation, promoted H9c2 cell proliferation, reduced ROS accumulation, and suppressed mitophagy. CD36 knockdown showed opposite effects to HIF-1α knockdown, which were reversed by palmitic acid. The HIF-1α activator dimethyloxalylglycine reversed the inhibitory effect of Parkin knockdown on mitophagy. In MCT-induced rats, the HIF-1α antagonist 2-methoxyestradiol (2ME) reduced RVSP, RVHI, pulmonary artery remodeling, lipid accumulation, and mitophagy. Recombinant CD36 abolished the therapeutic effect of 2ME but inhibited mitophagy. Activation of Parkin/PINK1 by salidroside (Sal) promoted mitophagy to ameliorate the pathological features of PAH-like rats, and 2ME further enhanced the therapeutic outcome of Sal. Conclusion PI3K p85α/HIF-1α induced CD36-mediated fatty acid uptake and Parkin/PINK1-dependent mitophagy to accelerate the progression of experimental PAH. Graphical Abstract

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PIK-24 Inhibits RSV-Induced Syncytium Formation via Direct Interaction with the p85α Subunit of PI3K

Abstract: PI3K protein has many functions and regulates various cellular processes. As an important regulatory subunit of PI3K, p85α can regulate the activity of PI3K signaling.

Cited by 3 publications

References 59 publications

PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A

PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A

Natural killer cell migration in HIV-infected individuals is inhibited by impairment of HIF-1α-mediated glycolysis

PI3K p85α/HIF-1α accelerates the development of pulmonary arterial hypertension by regulating fatty acid uptake and mitophagy

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