Ask about this productRelated genes to: PYCR2 antibody
- Gene:
- PYCR2 NIH gene
- Name:
- pyrroline-5-carboxylate reductase 2
- Previous symbol:
- -
- Synonyms:
- P5CR2
- Chromosome:
- 1q42.12
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-11
- Date modifiied:
- 2018-06-04
Related products to: PYCR2 antibody
Related articles to: PYCR2 antibody
- Proline metabolism is selectively altered in cancer cells, providing ATP, redox balance, and proline for cell growth. The final enzyme of proline biosynthesis is Δ-pyrroline-5-carboxylate (P5C) reductase (PYCR), which catalyzes the NAD(P)H-dependent reduction of P5C to proline. Humans have three PYCR isoforms, PYCR1 and PYCR2 in the mitochondrion and PYCR3 in the cytosol. Interest in developing selective inhibitors of PYCR enzymes has significantly increased over the past decade. Orthosteric inhibitors of PYCR1 have been developed, but they may lack specificity given the near identity of the active sites of PYCR1 and PYCR2. Here, we explored a new strategy of targeting noncatalytic cysteines to gain isoform selectivity. Initial results with iodoacetamide showed higher inhibition of PYCR2 relative to PYCR1, a result that was further explored with the thiol-reactive compound ebselen. Ebselen treatment resulted in a complete loss of PYCR2 activity with an IC value of 22 nM, which is 10-fold more sensitive than with PYCR1. Results from protection assays with dithiothreitol, site-directed mutagenesis, and mass spectrometry implicate Cys232 in PYCR2 as the target of ebselen. A new crystal structure of PYCR2 shows that Cys232 is in the P5C-binding loop, whereas PYCR1 contains a serine at this position. Our study provides new insight into the structural and functional roles of unique cysteine residues in PYCR2. Further, our results demonstrate proof-of-concept for targeting a noncatalytic cysteine as a new approach for selectively inhibiting PYCR2 over PYCR1. - Source: PubMed
Publication date: 2026/04/21
Rossman Tyrell CMeeks Kaylen RPurohit GunjanNaldrett Michael JTanner John JBecker Donald F - The functional significance of Chromosome 1 open reading frame 35 (C1orf35) in colorectal cancer (CRC) remains poorly characterized. This study investigates its oncogenic role and underlying mechanisms. We report that C1orf35 is frequently upregulated in CRC clinical specimens, and its elevated expression correlates strongly with advanced tumor stage and serves as an independent prognostic indicator for reduced overall survival. Functional assays, including experiments in patient-derived organoids, demonstrate that C1orf35 is essential for driving tumor cell proliferation, migration, and expansion. Mechanistically, we identify C1orf35 as an upstream activator of the transcription factor c-Myc. This activation triggers the transcriptional upregulation of the metabolic enzyme pyrroline-5-carboxylate reductase 2 (PYCR2), a key node in proline biosynthesis that facilitates tumor growth. Furthermore, we uncover a distinct, non-cell-autonomous function of C1orf35 in shaping the tumor immune microenvironment. Through c-Myc, C1orf35 impairs the cytotoxic function of tumor-infiltrating CD8 T cells. This inverse spatial relationship between C1orf35 expression and CD8 T-cell infiltration is validated by multiplex immunohistochemistry in human CRC tissues. Thus, our work defines C1orf35 as a dual-function oncoprotein that promotes CRC progression by coordinately enhancing tumor-intrinsic growth via the c-Myc/PYCR2 axis and fostering an immune-suppressive niche. These findings nominate C1orf35 as a promising multi-faceted therapeutic target and prognostic biomarker in CRC. - Source: PubMed
Publication date: 2026/03/28
Zhang ShaosenYang ChangjiangXu XunyeLan LanHe ZiyiChen JiaotingWang Caihong - Colorectal cancer (CRC) progression entails coordinated gene dysregulation and rewiring of signaling networks. Here, we investigated whether prefoldin subunit 2 (PFDN2) contributes to CRC progression by stabilizing pyrroline-5-carboxylate reductase 2 (PYCR2) and thereby modulating Wnt/β-catenin signaling. Integrated analyses of TCGA-COAD/READ and other public datasets showed that PFDN2 and PYCR2 are upregulated in CRC, positively correlated, and associated with poorer prognosis. These findings were corroborated in a 30-pair immunohistochemistry (IHC) cohort, and target modulation was confirmed by quantitative real-time PCR and Western blotting. Gain- and loss-of-function studies showed that PFDN2 promotes, whereas its knockdown suppresses, CRC cell proliferation and migration in vitro; in vivo, PFDN2 silencing reduced xenograft growth and Ki-67/β-catenin expression. PYCR2 was likewise elevated in CRC, linked to adverse clinicopathologic features, and enhanced proliferative and migratory phenotypes. Mechanistically, co-immunoprecipitation and immunofluorescence analyses revealed a PFDN2–PYCR2 interaction with predominantly cytoplasmic colocalization. PFDN2 manipulation altered PYCR2 protein but not mRNA levels; cycloheximide chase and MG132 rescue experiments indicated that PFDN2 stabilizes PYCR2 by limiting proteasome-dependent degradation. PFDN2 or PYCR2 depletion reduced TOP/FOPflash reporter activity, nuclear β-catenin accumulation, and expression of canonical Wnt targets, whereas PYCR2 re-expression partially restored these readouts and migratory capacity in PFDN2-silenced cells. Pharmacologic inhibition of canonical Wnt/β-catenin signaling attenuated the pro-proliferative and pro-migratory effects of PFDN2 or PYCR2 overexpression. The PFDN2–PYCR2–Wnt/β-catenin axis appears to be involved in CRC progression, and both proteins may have potential value as prognostic biomarkers and as candidates for further investigation as therapeutic targets. - Source: PubMed
Publication date: 2026/02/09
Chang XinChen PanLi LingCao JinzhongHou ShaohuaLi Hai - Colorectal cancer (CRC) remains a leading cause of cancer-related mortality globally, with poor survival outcomes in advanced stages due to therapy resistance and metastasis. While long non-coding RNAs (lncRNAs) are emerging as key regulators of CRC progression, their functional interplay and metabolic implications remain poorly understood. Here, we identified LINC02878 as a novel oncogenic lncRNA significantly upregulated in CRC and correlated with poor prognosis. Mechanistically, LINC02878 binds to the ZNF282 to activate PYCR2 expression, thereby enhancing proline biosynthesis and driving tumor aggressiveness. In vivo, LINC02878 knockdown suppressed subcutaneous tumor growth, reduced lung metastasis, and improved survival in xenograft models. Our study unveils the LINC02878/ZNF282/PYCR2/proline axis as a critical metabolic vulnerability in CRC, offering potential therapeutic targets for intervention. - Source: PubMed
Publication date: 2025/12/02
Lei Jun-PingWang LinWang Tian-YangLin Bing-HuXu YanShang SongXia TianGong Min-MingGuo YuFu JiaLi Yuan-Lin - Mammalian primordial germ cells (PGCs) migrate asynchronously through the embryonic hindgut and dorsal mesentery to reach the gonads. We previously found that interaction with different somatic niches regulates mouse PGC proliferation along the migration route. To characterize transcriptional heterogeneity of migrating PGCs and their niches, we performed single-cell RNA sequencing of 13,262 mouse PGCs and 7868 surrounding somatic cells during migration (E9.5, E10.5, E11.5) and in anterior vs posterior locations to enrich for leading and lagging migrants. Analysis of PGCs by position revealed dynamic gene expression changes between faster or earlier migrants in the anterior and slower or later migrants in the posterior at E9.5; these differences include migration-associated actin polymerization machinery and epigenetic reprogramming-associated genes. We furthermore identified changes in signaling with various somatic niches, notably strengthened interactions with hindgut epithelium via non-canonical WNT (ncWNT) in posterior PGCs compared to anterior. Reanalysis of a previously published dataset suggests that ncWNT signaling from the hindgut epithelium to early migratory PGCs is conserved in humans. Trajectory inference methods identified putative differentiation trajectories linking cell states across timepoints and from posterior to anterior in our mouse dataset. At E9.5, we mainly observed differences in cell adhesion and actin cytoskeletal dynamics between E9.5 posterior and anterior migrants. At E10.5, we observed divergent gene expression patterns between putative differentiation trajectories from posterior to anterior, including Nodal signaling response genes and and reprogramming factors and . At E10.5, we experimentally validated anterior migrant-specific upregulation via whole-mount immunofluorescence staining for LEFTY1/2 and phosphorylated SMAD2/3, suggesting that elevated autocrine Nodal signaling in migrating PGCs occurs as they near the gonadal ridges. Together, this positional and temporal atlas of mouse PGCs supports the idea that niche interactions along the migratory route elicit changes in proliferation, actin dynamics, pluripotency, and epigenetic reprogramming. - Source: PubMed
Publication date: 2025/11/19
Jaszczak Rebecca GarrettZussman Jay WWagner Daniel ELaird Diana J