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Title: Structural and functional characterisation of MS1
Author: Zaleska, Mariola Krystyna
ISNI:       0000 0004 5368 0206
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2014
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MS1 (Myocyte stress 1) is a muscle specific protein, implicated in the development of cardiac muscle hypertrophy. In rat models of induced left ventricular hypertrophy, MS1 expression is increased 3 times after applying stress signal with a peak expression before day 1. It may suggest that MS1 can act as a very important stress sensor that correlates external signals with a cellular response, however its complete mode of action needs to be further elucidated. It is has been proposed that MS1 is indirectly involved in gene expression regulation through a mechanism that involves actin dynamics and SRF. However, this work will show evidence that MS1 could be directly involved in gene expression regulation through a binding of specific DNA sequences. Based on our previous structural data it was found that MS1 contains a winged helix-turn-helix domain (WHTH), a common DNA binding domain present in transcription factors. Consequently, we hypothesised that MS1 could be a DNA binding protein itself and potentially it could act as a transcription factor. This work shows that MS1 possesses almost all characteristics of a transcription factor such as presence of a DNA binding domain, nuclear localisation and binding of a specific DNA sequence. In Chapter 3 a detailed subcellular localisation of MS1 will be characterised and it will provide evidence that MS1 cytoplasmic/nuclear localisation is more complex than anticipated and that it depends on a developmental stage as well as on environmental conditions such as presence of stress factors. In Chapter 4 DNA binding properties of MS1 will be characterised and ultimately it will be shown that MS1 binds to a defined DNA sequence in a manner typical of a winged helix-turn-helix domain. The findings of this thesis expand the present knowledge about MS1 function, where apart from its involvement in actin dynamics regulation it binds DNA opening up the possibility that it may be directly involved in gene expression regulation via acting as a transcription factor.
Supervisor: Pfuhl, Mark Christoph Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available