A thesis submitted to the Faculty of Science, University of Witwatersrand,
Johannesburg, South Africa, in fulfilment of the requirements for the Degree of Doctor of Philosophy, This thesis presented as a series of manuscripts
1993 / In this study the morphologic, cytokinetic, biochemical, and molecu1w:
consequences of low-dose continuous Puromycin-exposure were examined in
HL-60 cells, and in a variety of malignant and non-malignant human and
murine cell types. Puromycin (PM) is a composite of the amino nucleoside
dimethyladenosine and tyrosine-o-methylether. Functionally it is an analogue
of the terminal aminoacyl-adenosine portion of aminoacyl-tRNA, more
specifically of tyrosyl..tRNA. At high concentrations 5-S0#tg/ml (10-100#tM)
PM has been found to block protein synthesis completely by causing the
premature release from the ribosomes of truncated peptide chains which are
bound to PM through their carboxyl termini.
The nascent PMGpeptide
complexes (PMPs) are rapidly degraded through a ubiquitin-dependent
pathway and are of interest because of (i) their potential to compete for
degradation with the natural substrates of the ubiquitin-dependent pathway,
including cyclin B, and (ii) because their structure predicts an inhibitory effect
on tyrosine kinase activity. In the current' study then, special consideration
was given to the effect of PM on the cell cycle, on apoptosis (programmed. cell
death), and on tyrosine kinase activity, As a means of comparison, certain of
these effects were also examined with respect to another translation inhibitor
Cycloheximide (CHX), to two other substituted purines Puromycin
Amino nucleoside (PAN) and 6..Dimethylaminopurine (6-DMAP), as well as to
the cyclophospbamide derivative Mafosfamide (ASTA Z 7557). / GR2017
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/21756 |
| Date | January 1993 |
| Creators | Davidoff, Avri Nava |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | Online resource (220 leaves), application/pdf |
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