Scpep1,也称为RISC或Serine Carboxypeptidase 1,是一种重要的溶酶体丝氨酸羧肽酶。Scpep1在细胞内被加工成成熟的二聚体,由35 kDa的N端片段和未知的18 kDa的C端片段组成。Scpep1在多种组织中广泛表达,包括胚胎心脏和血管、成年小鼠的主动脉平滑肌细胞和内皮细胞等。Scpep1在肾脏中主要表达于近端肾小管上皮细胞,并在溶酶体中富集。Scpep1的活性需要经过蛋白水解加工[2]。
Scpep1在多种生物学过程中发挥作用。研究发现,Scpep1在调节血管内皮生长因子(VEGF)表达和细胞增殖中发挥重要作用。在缺氧条件下,Scpep1的表达增加,并通过抑制NF-κB/VEGF和TGF-β2/VEGF信号通路保护细胞免受损伤[3][4]。此外,Scpep1还与细胞增殖相关,Scpep1缺陷小鼠表现出角膜云翳和皮肤增厚等异常表现[1]。
Scpep1的表达受到多种因素的调控。研究发现,全反式视黄酸(ATRA)可以刺激Scpep1的表达,并通过抑制NF-κB和TGF-β2信号通路保护细胞免受缺氧诱导的损伤[3][4]。此外,Scpep1的表达还与多能性相关。研究发现,Scpep1在胚胎发育早期表达,并与多能性状态相关[5]。Scpep1的表达还与猪的肌肉脂肪含量相关[6]。
综上所述,Scpep1是一种重要的溶酶体丝氨酸羧肽酶,在细胞内被加工成成熟的二聚体,并在多种组织中广泛表达。Scpep1在调节VEGF表达、细胞增殖和多能性等方面发挥重要作用,并受到多种因素的调控。Scpep1的研究有助于深入理解其在细胞生物学和疾病发生中的作用机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Pan, Xuefang, Wang, Yanting, Lübke, Torben, Hinek, Aleksander, Pshezhetsky, Alexey V. 2017. Mice, double deficient in lysosomal serine carboxypeptidases Scpep1 and Cathepsin A develop the hyperproliferative vesicular corneal dystrophy and hypertrophic skin thickenings. In PloS one, 12, e0172854. doi:10.1371/journal.pone.0172854. https://pubmed.ncbi.nlm.nih.gov/28234994/
2. Lee, Ting-Hein D, Streb, Jeffrey W, Georger, Mary A, Miano, Joseph M. 2006. Tissue expression of the novel serine carboxypeptidase Scpep1. In The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 54, 701-11. doi:. https://pubmed.ncbi.nlm.nih.gov/16461364/
3. Xu, Yong, Gao, Ai-Mei, Ji, Li-Juan, Li, Hai-Lun, Zheng, Dong-Hui. 2016. All-Trans Retinoic Acid Attenuates Hypoxia-Induced Injury in NRK52E Cells via Inhibiting NF-x03BA;B/VEGF and TGF-β2/VEGF Pathway. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 38, 229-36. doi:10.1159/000438624. https://pubmed.ncbi.nlm.nih.gov/26783748/
4. Wan, X, Li, X, Bo, H, Yin, Z, Cao, C. 2012. All-trans retinoic acid protects renal tubular epithelial cells against hypoxia induced injury in vitro. In Transplantation proceedings, 45, 497-502. doi:10.1016/j.transproceed.2012.02.030. https://pubmed.ncbi.nlm.nih.gov/23267795/
5. Bernardo, Andreia S, Jouneau, Alice, Marks, Hendrik, Pedersen, Roger A, Dinnyes, Andras. 2018. Mammalian embryo comparison identifies novel pluripotency genes associated with the naïve or primed state. In Biology open, 7, . doi:10.1242/bio.033282. https://pubmed.ncbi.nlm.nih.gov/30026265/
6. Davoli, R, Luise, D, Mingazzini, V, Serra, A, Russo, V. 2015. Genome-wide study on intramuscular fat in Italian Large White pig breed using the PorcineSNP60 BeadChip. In Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie, 133, 277-82. doi:10.1111/jbg.12189. https://pubmed.ncbi.nlm.nih.gov/26578072/