SCAF1

Last update 08 May 2025

Basic Info

Synonyms

FLJ00034, SCAF, SCAF1

+ [9]

Introduction

May function in pre-mRNA splicing.

100 Clinical Results associated with SCAF1

100 Translational Medicine associated with SCAF1

0 Patents (Medical) associated with SCAF1

131

Literatures (Medical) associated with SCAF1

01 Mar 2025·Journal for ImmunoTherapy of Cancer

PLS-α-GalCer: a novel targeted glycolipid therapy for solid tumors

Article

Author: Kularatne, Ruvanthi N ; Tiwary, Shweta ; Berzofsky, Jay A ; Skoczen, Sarah L ; Burks, Julian ; Stevens, David M ; Stern, Stephan T

BackgroundThe prototypical type I natural killer T (NKT) cell agonist, α-galactosylceramide (α-GalCer), has shown only minimal effects against solid tumors in the clinic. The most promising clinical application of α-GalCer currently entails ex vivo priming of patient-derived dendritic cells; however, this technology suffers from cost, logistical concerns, and safety issues. As a parenteral dendritic cell-targeted alternative, we demonstrate that poly(L-lysine succinylated) (PLS)-α-GalCer, a novel scavenger receptor-A1 targeted α-GalCer prodrug has enhanced antitumor activity compared with α-GalCer.MethodsTo compare the antitumor activity of PLS-α-GalCer and α-GalCer, we used mouse syngeneic subcutaneous pancreatic and cervical tumor models using Panc02 and TC-1 cells, respectively. Intratumoral immune cell infiltration was evaluated using flow cytometry and immunohistochemistry whole-slide scan analysis. Serum cytokine levels were examined by ELISA and LEGENDplex analysis. Type I NKT cell intracellular interferon-gamma (IFN-γ) levels were determined by flow cytometry. Immunofluorescence was used to test the uptake and processing of PLS-α-GalCer and α-GalCer in antigen-presenting cells (APCs).ResultsThe scavenger receptor A1 (SR-A1)-mediated targeting of α-GalCer to APCs by PLS-α-GalCer significantly improves the antitumor function against solid tumors compared with α-GalCer. The Panc02 and TC-1 tumor models demonstrated that PLS-α-GalCer increases intratumoral antigen-specific T, NKT and T cells, and increases the M1/M2 macrophage ratio. In the TC-1 tumor model, we demonstrated that PLS-α-GalCer synergizes with an E7 tumor vaccine to significantly suppress tumor growth and increase the survival of mice. Furthermore, the antitumor function of PLS-α-GalCer is dependent on type I NKT cells and requires SR-A1 targeting. In addition, using SR-A1 knockout RAW cells, a murine macrophage cell line, we showed that PLS-α-GalCer uptake and processing in APCs are more efficient compared with α-GalCer. PLS-α-GalCer also induces significantly less serum Th2 and Th17 cytokines while stimulating significantly more IFN-γ for a longer period and increases Th1:Th2 cytokine ratios compared with α-GalCer.ConclusionsPLS-α-GalCer is a promising immunotherapy for the treatment of solid tumors that has superior antitumor activity compared with α-GalCer and could be combined with tumor vaccines and potentially other immunotherapies such as immune checkpoint inhibitors.

08 Feb 2025·Nucleic Acids Research

Phenotypic screens identify SCAF1 as critical activator of RNAPII elongation and global transcription

Article

Author: Eilers, Martin ; Wolf, Elmar ; Lamer, Stephanie ; Eilers, Ursula ; Schülein-Völk, Christina ; Wenzel, Julia ; Erhard, Florian ; Bhandare, Pranjali ; Rummel, Teresa ; Hofstetter, Julia ; Narain, Ashwin ; Schlosser, Andreas

AbstractTranscripts produced by RNA polymerase II (RNAPII) are fundamental for cellular responses to environmental changes. It is therefore no surprise that there exist multiple avenues for the regulation of this process. To explore the regulation mediated by RNAPII-interacting proteins, we used a small interfering RNA (siRNA)-based screen to systematically evaluate their influence on RNA synthesis. We identified several proteins that strongly affected RNAPII activity. We evaluated one of the top hits, SCAF1 (SR-related C-terminal domain-associated factor 1), using an auxin-inducible degradation system and sequencing approaches. In agreement with our screen results, acute depletion of SCAF1 decreased RNA synthesis, and showed an increase of Serine-2 phosphorylated-RNAPII (pS2-RNAPII). We found that the accumulation of pS2-RNAPII within the gene body occurred at GC-rich regions and was indicative of stalled RNAPII complexes. The accumulation of stalled RNAPII complexes was accompanied by reduced recruitment of initiating RNAPII, explaining the observed global decrease in transcriptional output. Furthermore, upon SCAF1 depletion, RNAPII complexes showed increased association with components of the proteasomal-degradation machinery. We concluded that in cells lacking SCAF1, RNAPII undergoes a rather interrupted passage, resulting in intervention by the proteasomal-degradation machinery to clear stalled RNAPII. While cells survive the compromised transcription caused by absence of SCAF1, further inhibition of proteasomal-degradation machinery is synthetically lethal.

01 Feb 2025·Journal of Investigative Medicine

Plasma from type 1 diabetes patients promotes pro-atherogenic cholesterol transport in human macrophages

Article

Author: Reiss, Allison B ; Kasselman, Lora J ; Voloshyna, Iryna ; Srivastava, Ankita ; Levine, Robert L ; Renna, Heather A ; Mejia-Corletto, Jorge ; De Leon, Joshua ; Accacha, Siham

Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits RCT by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HCs) and 20 patients with type 1 diabetes mellitus (T1DM), 10–19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, and 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, and CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of N-(carboxymethyl)-lysine-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells’ uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized low-density lipoprotein. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.

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SCAF1

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