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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Regulation of the pro-apoptotic protein Bax

Cross, Justin Robert January 2006 (has links)
Apoptosis is essential for correct development and tissue homeostasis of multi-cellular organisms as well as providing a critical safety mechanism to remove unwanted and damaged cells throughout life. Apoptosis is also relevant to human pathologies: many cancers acquire lesions in apoptotic pathways whilst inappropriate activation of apoptosis occurs in degenerative disease. This thesis studies the regulation and function of a key regulator of apoptosis and mitochondrial dysfunction, the Bcl-2 family member, Bax. Bax is shown to be a cytoplasmic protein that, upon activation, rapidly translocates into mitochondrially-associated foci. The timing and possible causes of Bax activation have been studied. Live cell video microscopy reveals that this is a rapid and co-ordinated process and is accompanied by loss of the mitochondrial membrane potential. Two viral proteins, El B 19k from Adenovirus and BHRF1 from Epstein Bar Virus, are shown to block Bax activation at different steps. Using these proteins it is shown that changes in mitochondrial ultrastructure occur prior to Bax activation. In the second part of this thesis, a structure / function analysis of the Bax protein leads to the identification of a novel mutation that promotes its activation. Subsequently, this mutation is used, in combination with El B 19k, in a proteomic strategy to isolate and identify candidate Bax interacting proteins at a critical step in the protein's activation. The results of this, and a similar screen with another Bcl-2 family protein, Bcl-XL, are reported. The data set contains known interacting proteins and proteins previously implicated in apoptosis control. In addition a range of metabolic and transport proteins not previously implicated in the control of Bcl-2 family proteins are identified and their relevance discussed.
2

Regulation of class IA phosphoinositide 3-kinase signalling enzymes by post-translational modifications, protein interactions and absolute protein expression levels

Geering, Barbara January 2006 (has links)
Phosphoinositide 3-kinases (PI3Ks) are signal transduction proteins that regulate a wide range of cellular processes. A key subset of PI3Ks are the so-called class IA enzymes consisting of a p85 regulatory and p110 catalytic subunit. While the biological activities of PI3Ks have been investigated in detail, the biochemical mechanism of their regulation is underexplored. We therefore strived to investigate post-translational modifications and absolute protein levels of class IA PI3Ks using electrophoresis and mass spectrometry (MS). We thereby focused on endogenous PI3K subunits and physiological stimulation. Modifications including amino acid substitutions, phosphorylation and hydroxylation were detected in the regulatory subunit of unstimulated cells. While modifications in p85 were unaltered following cellular stimulation, dynamic changes in the tyrosine phosphorylation of the catalytic subunit p1105 were detected upon B cell stimulation. p1105 tyrosine phosphorylation does not appear to be critical for intrinsic PI3K lipid kinase activity, but might have a role in the interaction of p110S with known and novel potential PI3K partners identified by MS. However, identification of modified amino acid residues by MS turned out to be challenging, also because p110 proteins could not be resolved by 2D-gel electrophoresis. An important question in the PI3K field is whether class IA subunits can exist as monomers. It has been reported that p85 is present in excess over p110 and suggested that monomeric p85 has a negative role in the regulation of PI3K activity. Our analysis of class IA PI3K protein expression, amongst other by affinity and ion exchange chromatography, does not support this notion. In summary, our work has revealed dynamic changes in the post-translational modification of the p110 (but not p85) and their interaction with partners. The ratio of p110 to p85, however, does not seem to be as dynamic, with equal amounts of p85 to p110 under all conditions investigated.
3

Interactions of BspMI with two asymmetric sequences

Kingston, Isabel Jane January 2004 (has links)
No description available.
4

Isolation and identification of imidazoline-2 binding proteins

Kimura, Atsuko January 2004 (has links)
No description available.
5

The MUS81 family of proteins

Ciccia, Alberto January 2006 (has links)
The faithful and complete replication of DNA is necessary for the maintenance of genome stability. The endonuclease MUS81 has recently been implicated in the repair of blocked forks during DNA replication. MUS81 is related to the nucleotide excision repair proteins XPF and ERCC1, due to the common ERCC4 nuclease domain that they share. Based on database searches for proteins containing the ERCC4 domain, we have identified four novel members of the MUS81 family. We named two of them EME1 and EME2, because of their similarity with S. pombe Eme1 protein. We showed that EME1 and EME2 interact with MUS81 and that MUS81/EME1 and MUS81/EME2 complexes are endonucleases that exhibit a high specificity for synthetic replication fork and 3'-flap structures in vitro. In particular, the MUS81/EME2 heterodimer is 10-fold more active than MUS81/EME1. Besides EME1 and EME2, we have identified two additional proteins of the MUS81 family, HEF and HIP. HEF, also referred to as FANC-M, is a 250 kDa protein that is associated with the genetic disorder of Fanconi Anemia. HIP (HEF Interacting Protein) is a novel 24 KDa protein interacting with HEF/FANC-M. We showed that HIP forms a complex with HEF/FANC-M both in vitro and in vivo and that it is part of the Fanconi Anemia core complex. HEF/FANC-M contains a DEAH helicase domain, which is required for translocase activity, and an ERCC4 nuclease domain. We showed that the ERCC4 nuclease domain of HEF/FANC-M is inactive, as suggested by sequence analysis. Based on the similarity with other members of the MUS81 family, we propose a role for the complex between HEF/FANC-M and HIP in recognising branched DNA structures, which could arise after DNA replication fork blockage. Therefore, HEF/FANC-M and HIP may be involved in targeting the Fanconi Anemia core complex to blocked replication forks.
6

Studies of a 'Bacillus subtilis' multifunctional regulatory protein sinR

Leejeerajumnean, Suporn January 2001 (has links)
No description available.
7

Defining the physiological role of phosphatidylinositol 3-kinase protein kinase activity

Foukas, Lazaros January 2003 (has links)
No description available.
8

Immunological effects of extracellular calreticulin

Watson, Vivien January 2005 (has links)
No description available.
9

A mechanism of membrane neutral lipid acquisition by the microsomal triglyceride transfer protein

Read, Jacqueline January 2001 (has links)
No description available.
10

Characterisation of a novel zinc finger protein as an oestrogen receptor {220} co-regulator

Lopez Garcia, Jorge January 2005 (has links)
No description available.

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