Charakterisierung einer unbekannten Interaktionsregion im Aminoterminus des Transkriptionsfaktors STAT1

by Grace Wen
Doctoral thesis
Date of Examination:2025-07-09
Date of issue:2025-06-26
Advisor:Prof. Dr. Thomas Meyer
Referee:Prof. Dr. Thomas Meyer
Referee:Prof. Dr. Dieter Kube
Persistent Address: http://dx.doi.org/10.53846/goediss-11353

 

 

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Abstract

English

This study investigates the roles of two amino acid residues, H58 and R70, in the N-terminal domain of the signal transducer and activator of transcription 1 (STAT1) in the context of JAK-STAT pathway activation following cytokine stimulation. While the H58A mutation had no significant effect compared to wild-type STAT1, the R70A mutation led to increased tyrosine phosphorylation, enhanced DNA binding, and prolonged nuclear accumulation. These changes were associated with increased reporter gene expression using a synthetic promoter, though no global transcriptional differences were observed by RT-PCR. The findings suggest that R70 contributes to stabilizing the antiparallel dimer conformation of STAT1. Its mutation may favor the transcriptionally active, parallel dimer form by disrupting electrostatic interactions, thus altering STAT1 function.
Keywords: STAT1; JAK-STAT pathway; Signal transducer and activator of transcription