Ask about this productRelated genes to: PQLC2 Blocking Peptide
- Gene:
- PQLC2 NIH gene
- Name:
- PQ loop repeat containing 2
- Previous symbol:
- -
- Synonyms:
- FLJ20320, SLC66A1
- Chromosome:
- 1p36.13
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-14
- Date modifiied:
- 2018-06-26
Related products to: PQLC2 Blocking Peptide
Related articles to: PQLC2 Blocking Peptide
- The discovery of bifunctional degradation activating compounds (BiDACs) has led to the development of a new class of drugs that promote the clearance of their protein targets. BiDAC-induced ubiquitination is generally believed to direct cytosolic and nuclear proteins to proteolytic destruction by proteasomes. However, pathways that govern the degradation of other classes of BiDAC targets, such as integral membrane and intraorganellar proteins, have not been investigated in depth. In this study we use morphological profiling and CRISPR/Cas9 genetic screens to investigate the mechanisms by which BiDACs induce the degradation of plasma membrane receptor tyrosine kinases (RTKs) EGFR and Her2. We find that BiDAC-dependent ubiquitination triggers the trafficking of RTKs from the plasma membrane to lysosomes for degradation. Notably, functional proteasomes are required for endocytosis of RTKs upstream of the lysosome. Additionally, our screen uncovers a non-canonical function of the lysosome-associated arginine/lysine transporter PQLC2 in EGFR degradation. Our data show that BiDACs can target proteins to proteolytic machinery other than the proteasome and motivate further investigation of mechanisms that govern the degradation of diverse classes of BiDAC targets. - Source: PubMed
Publication date: 2025/05/10
Villa SammyJafri QumberLazzari-Dean Julia RSangha ManjotOlsson NiclasLefebvre Austin E Y TFitzgerald Mark EJackson KatrinaChen ZhenghaoFeng Brian YNile Aaron HStokoe DavidBersuker Kirill - Efferocytosis in macrophages typically engages an anti-inflammatory positive feedback regulatory mechanism. In osteoarthritis (OA), characterized by imbalanced inflammatory homeostasis, the proinflammatory state of macrophages in the immune microenvironment can be reversed through enhanced efferocytosis. This study develops an in situ proefferocytosis hydrogel microsphere (macrophage polarity converter, H-C@IL) for OA treatment. Immunoliposomes (IL), CD16/32 antibody-modified clodronate liposomes, are initially prepared using the Re-emulsion method. Then, the IL is loaded into CCL19-modified HAMA microspheres through microfluidic technology. In vitro, H-C@IL can specifically recruit M0 and M1 macrophages via CCL19, induce apoptosis in M1 macrophages through secondary targeting with IL, and provide "Find/Eat-me" signals to enhance in situ efferocytosis. Additionally, it promotes macrophage polarization toward the M2 phenotype. In vivo, behavioral, imaging, and histological analyses demonstrate that H-C@IL effectively facilitates macrophage polarization toward M2, inhibits inflammation, and promotes cartilage regeneration. Mechanistically, H-C@IL enhances efferocytosis by activating proteins such as PROS1 and TIMD4 in M0 macrophages. Concurrently, signaling pathways, including PQLC2-Arg-Rac1 and Pbx1/IL-10, are activated to drive the polarization of macrophages from M0 to M2. In summary, H-C@IL promotes M0 macrophage efferocytosis in situ, facilitates macrophage polarization toward M2, restores inflammatory homeostasis, and promotes cartilage regeneration, offering a comprehensive treatment strategy for OA. - Source: PubMed
Publication date: 2025/01/09
Wang YongPu ChaoyuHan ZeyuDu YaweiChen LiangHuang YanranLuo YueXiang ChaoHe JiangtaoChen LuCui WenguoJiang KeLi Yuling - Amino acid pools in the cell are monitored by dedicated sensors, whose structures are now coming into view. The lysosomal Rag GTPases are central to this pathway, and the regulation of their GAP complexes, FLCN-FNIP and GATOR1, have been worked out in detail. For FLCN-FNIP, the entire chain of events from the arginine transporter SLC38A9 to substrate-specific mTORC1 activation has been visualized. The structure GATOR2 has been determined, hinting at an ordering of amino acid signaling across a larger size scale than anticipated. The centerpiece of lysosomal signaling, mTORC1, has been revealed to recognize its substrates by more nuanced and substrate-specific mechanisms than previous appreciated. Beyond the well-studied Rag GTPase and mTORC1 machinery, another lysosomal amino acid sensor/effector system, that of PQLC2 and the C9orf72-containing CSW complex, is coming into structural view. These developments hold promise for further insights into lysosomal physiology and lysosome-centric therapeutics. - Source: PubMed
Publication date: 2023/02/16
Cui ZhichengJoiner Aaron M NJansen Rachel MHurley James H - Metabolic homeostasis requires dynamic catabolic and anabolic processes. Autophagy, an intracellular lysosomal degradative pathway, can rewire cellular metabolism linking catabolic to anabolic processes and thus sustain homeostasis. This is especially relevant in the liver, a key metabolic organ that governs body energy metabolism. Autophagy's role in hepatic energy regulation has just begun to emerge and autophagy seems to have a much broader impact than what has been appreciated in the field. Though classically known for selective or bulk degradation of cellular components or energy-dense macromolecules, emerging evidence indicates autophagy selectively regulates various signaling proteins to directly impact the expression levels of metabolic enzymes or their upstream regulators. Hence, we review three specific mechanisms by which autophagy can regulate metabolism: A) nutrient regeneration, B) quality control of organelles, and C) signaling protein regulation. The plasticity of the autophagic function is unraveling a new therapeutic approach. Thus, we will also discuss the potential translation of promising preclinical data on autophagy modulation into therapeutic strategies that can be used in the clinic to treat common metabolic disorders. - Source: PubMed
Publication date: 2021/07/28
Byrnes KatherineBlessinger SophiaBailey Niani TiayeScaife RussellLiu GangKhambu Bilon - - Source: PubMed
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