Supplementary data to the Article: Proteasomal Activity and Disease-Outcome in Patients with Phenylketonuria, Carriers of a Structural SLC7A5 Variant

Zitation: Bik-Multanowski, Miroslaw: Supplementary data to the Article: Proteasomal Activity and Disease-Outcome in Patients with Phenylketonuria, Carriers of a Structural SLC7A5 Variant. 15. Oktober 2025. Open Data LMU. 10.5282/ubm/data.698

Be­schrei­bung

Treatment in phenylketonuria is aimed at protecting the brain from uncontrolled hyperphenylalaninemia. Although treatment methods are well established, clinical outcomes vary among patients. This may be due to alterations of phenylalanine transport mediated by the amino acid transporter LAT1, which also regulates the function of the mTORC1/proteasomal pathway. We explored the cellular mechanisms underlying potential phenotypic differences between carriers and noncarriers of the rs113883650 polymorphism – a marker of a structural variant of the SLC7A5 gene. For our experiments we used a model of hyperphenylalaninemia based on induced pluripotent stem cells (hiPSCs). We conducted a targeted analysis of the expression of peptides involved in the FOXO/proteasomal signaling pathway. We confirmed a statistically significant difference in FOXO pathway expression between the two groups of carriers and non carriers of the investigated variant (p = 0.005, t-test) under high Phe conditions. Notably, an increased abundance of CDK2 and ERK1 (MAPK1)—both known to downregulate FOXO1—was observed in carriers of rs113883650. We did not detect statistically significant differences between the tested groups under low Phe conditions.

Stichwörter

FOXO, Proteasome, Phenylketonuria, LAT1

• Dokumententyp: Daten
• Name der Kontakt­person: Bik-Multanowski, Miroslaw
• E-Mail der Kontaktperson: miroslaw.bikmultanowski at med.uni-muenchen.de
• Fächer: Medizin
• Dewey Dezimal­klassi­fikation: 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Eingestellt von: Prof. Miroslaw Bik-Multanowski