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Title: Identification and functional analysis of internal ribosome entry segments in Apaf-1 and BAG-1 mRNAs
Author: Coldwell, Mark J.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2000
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The apoptotic protease activating factor (Apaf-1) plays a central role in apoptosis: interaction of this protein with procaspase-9 leads to cleavage and activation of this initiator caspase. In common with other mRNAs whose protein products have a major regulatory function, the 5' untranslated region (UTR) of Apaf-1 is long, G-C rich and has the potential to form secondary structure. An internal ribosome entry segment (IRES) was identified in the 5' UTR of Apaf-1, located in a 233 nucleotide region towards the 3' end of the leader. The Apaf-1 IRES is active in several cell lines, although to differing degrees, which suggests an important requirement for non-canonical trans-acting factors in internal ribosome entry. BAG-1 (also known as RAP46/HAP46) was originally identified as a 46 kDa protein that bound to and enhanced the anti-apoptotic properties of Bcl-2. BAG-1 exists as three major isoforms (designated p50, p46 or BAG-1L, BAG-1M and BAG-1S respectively) that are translated from a common transcript. The 5' untranslated region upstream of the p36 open reading frame (ORF) is also long and G-C rich and analysis of this region indicated that the translation initiation of the most highly expressed isoform (p36/BAG-1S) can occur by both internal ribosome entry and by cap-dependent scanning. The BAG-1 IRES also exhibits different activity in several cell lines, but this does not correlate with the changes in BAG-1 isoform expression observed in transformed cells. Functional analysis of the Apaf-1 and BAG-1 IRESs shows that they are active during the early stages of apoptosis induced by TNF-related apoptosis inducing ligand (TRAIL).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available