2017年12月12日 · Whether SCP4 can be used as a drug target for diabetes therapeutics awaits comprehensive understanding of the role of SCP4 in pathophysiology. Is the expression or activity of SCP4 changed in metabolically active tissues like liver, skeletal muscle, adipose tissue, and pancreatic islets?

In this study, we discovered a nuclear phosphatase, SCP4/CTDSPL2 (SCP4), that dephosphorylated FoxO1/3a and promoted FoxO1/3a transcription activity. We found that SCP4 enhanced the transcription of FoxO1/3a target genes encoding PEPCK1 and G6PC, key enzymes in hepatic gluconeogenesis.

We found that SCP4 enhanced the transcription of FoxO1/3a target genes encoding PEPCK1 and G6PC, key enzymes in hepatic gluconeogenesis. Ectopic expression of SCP4 increased, while knockdown of SCP4 inhibited, glucose production.

SCP4 is a nuclear phosphatase expressed in skeletal muscle cells. SCP4 consists of a regulatory domain (amino acids 1–262), which contains two nuclear locations signaling (NLS), and a catalytic phosphatase domain (amino acids 263–466) that reportedly dephosphorylates Smad1/5 (Fig. 1a).

Knockdown of SCP4 significantly suppressed FoxO1/3a-mediated expression of Atrogin-1 and MuRF-1 and prevented muscle wasting in mice with CKD. Thus, SCP4 is a novel regulator of FoxO transcription factors and promotes cellular proteolysis.

2017年8月1日 · Upregulation of SCP4 enhances FoxO1/3a transcription activities by preventing their nuclear export; conversely, SCP4 inhibition in catabolic condition suppresses FoxO1/3a activity and hence muscle proteolysis in CKD.

Our findings underscore the critical role of SCP4 in regulating cartilage development and endochondral osteogenesis during embryonic development partially via inhibition of chondrocytes apoptosis regulated by FoxO3a dephosphorylation.

Since dephosphorylation of FoxOs regulates ubiquitin/ proteasome protein metabolism, we tested whether a novel nuclear phosphatase, the small C-terminal domain phosphatase (SCP) 4, regulates FoxOs signaling and, in turn, muscle wasting.

Whether SCP4 can be used as a drug target for diabetes therapeutics awaits comprehensive understanding of the role of SCP4 in pathophysiology. Is the expression or activity of SCP4 changed in metabolically active tissues like liver, skeletal …

2025年1月14日 · Foundation Universe Hub - For information on Sites, Mobile Task Forces, Departments, and more. Audio Adaptations - Links to audio read-outs of various articles on the site. SCP Series 4 - Tales Edition - Tales associated with SCPs of this Series. SCP-3009 - Hi, I'm Your Snappelganger! SCP-3043 - Murphy Law in… Type 3043 — FOR MURDER!