Oxygen-independent stabilization of HIF-2α in breast cancer through direct interaction with peptidyl-prolyl cis-trans isomerase NIMA-interacting 1

Guillen-Quispe, Yanymee N.; Kim, Su-Jung; Saeidi, Soma; Zhou, Tianchi; Zheng, Jie; Kim, Seong Hoon; Fang, Xizhu; Chelakkot, Chaithanya; Rios-Castillo, Milton E.; Shin, Young Kee; Surh, Young-Joon

doi:10.1016/j.freeradbiomed.2023.07.020

Cited by 5 publications

(3 citation statements)

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“…HIF is composed of two subunits: one alpha subunit of which there are three subtypes (HIF-1α, HIF-2α, HIF-3α) and one beta subunit (HIF-1β) [145]. The most prominently studied subunits are the oxygen-dependent alpha subunits HIF-1α and HIF-2α, which are both necessary for cancer cell viability in the hypoxic tumor microenvironment [84]. In normoxic conditions, HIF-1α is regulated by prolyl hydroxylase domain-containing proteins (PHD) and the Von Hippel-Lindau tumor suppressor protein (pVHL), which each coordinate to promote the rapid ubiquitination and degradation of HIF-1α [146].…”

Section: Pin1 Enhances Oncogenic Protein Stabilitymentioning

confidence: 99%

“…Additionally, Pin1 facilitates the sumoylation of PML by SUMO1 in glioma stem cells, which enables PML to interact with and stabilize c-Myc, thereby permitting the survival and carcinogenic potential of glioma stem cells [150]. Similarly, in HIF-2α, Pin1 directly binds to the subunit's phosphorylated Ser790 site located in the nuclear export signal domain [84]. Phosphorylation at this site is essential for the stability and transactivation of HIF-2α and enables its activity even in normoxic conditions, enabling the progression of breast cancer cells [84].…”

Section: Pin1 Enhances Oncogenic Protein Stabilitymentioning

confidence: 99%

“…Similarly, in HIF-2α, Pin1 directly binds to the subunit's phosphorylated Ser790 site located in the nuclear export signal domain [84]. Phosphorylation at this site is essential for the stability and transactivation of HIF-2α and enables its activity even in normoxic conditions, enabling the progression of breast cancer cells [84].…”

Section: Pin1 Enhances Oncogenic Protein Stabilitymentioning

confidence: 99%

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Pin1-Catalyzed Conformation Changes Regulate Protein Ubiquitination and Degradation

Jeong,

Usman,

et al. 2024

Cells

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The unique prolyl isomerase Pin1 binds to and catalyzes cis–trans conformational changes of specific Ser/Thr-Pro motifs after phosphorylation, thereby playing a pivotal role in regulating the structure and function of its protein substrates. In particular, Pin1 activity regulates the affinity of a substrate for E3 ubiquitin ligases, thereby modulating the turnover of a subset of proteins and coordinating their activities after phosphorylation in both physiological and disease states. In this review, we highlight recent advancements in Pin1-regulated ubiquitination in the context of cancer and neurodegenerative disease. Specifically, Pin1 promotes cancer progression by increasing the stabilities of numerous oncoproteins and decreasing the stabilities of many tumor suppressors. Meanwhile, Pin1 plays a critical role in different neurodegenerative disorders via the regulation of protein turnover. Finally, we propose a novel therapeutic approach wherein the ubiquitin–proteasome system can be leveraged for therapy by targeting pathogenic intracellular targets for TRIM21-dependent degradation using stereospecific antibodies.

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Section: Pin1 Enhances Oncogenic Protein Stabilitymentioning

confidence: 99%