Biennial Report 2011–2012

Department of Immunology and Cell Biology
the strains. We did not find any correlation between VLY production
level and G. vaginalis genotype/biotype. In contrast,
a link between G. vaginalis genotype and sialidase production
was established. Our findings on the diversity of VLY expression
level in different clinical isolates and linking sialidase activity
with the genotype of G. vaginalis could help to evaluate
the pathogenic potential of different G. vaginalis strains.
Figure 2. Detection of VLY production level in vivo. (a) Growth of six
Gardnerella vaginalis isolates over time. (b) Quantitation by ELISA
of VLY produced by six G. vaginalis clinical isolates at regular time
intervals during growth. Error bars represent 95% CI of mean, n = 3.
Reference: Pleckaityte et al., FEMS Immunol. Med. Microbiol.
2012, 65(1):69-77.
Regulation of hypoxia-inducible factor
HIF-3α expression via the alternative
pre-mRNA splicing mechanism.
Recent genome-wide analyses of alternative splicing indicate
that up to 70% of human genes may have alternative splice
forms, suggesting that alternative splicing together with various
posttranslational modifications plays a major role in the
production of proteome complexity.
Changes in splice-site selection have been observed in various
types of cancer and may affect genes implicated in tumor progression
and in susceptibility to cancer. This may lead to altered
efficiency of splice-site recognition, resulting in overexpression
or down-regulation of certain splice variants, a switch in splicesite
usage, or failure to recognize splice sites correctly, resulting
in cancer-specific splice forms. At least in some cases, changes
in splicing have been shown to play a functionally significant
role in tumorigenesis, either by inactivating tumor suppressors
or by gain of function of proteins promoting tumor development.
Thus, the identification of cancer specific splice forms
provides a novel source for the discovery of diagnostic or prognostic
biomarkers and tumor antigens suitable as targets for
therapeutic intervention.
Hypoxia has long been recognized as a common feature of solid
tumours and a negative prognostic factor for response to treatment
and survival of cancer patients. Biological responses to
hypoxia involve induction of transcription of a network of target
genes, a process which is coordinately regulated by hypoxia-inducible
transcription factors (HIFs). three structurally related
bHLH transcription factors (HIF-1, HIF-2 and HIF-3).
HIFs recognize hypoxia response elements of targets genes as
hetrodimeric complexes (HIF-1a, HIF-2a and HIF-3a) with
the transcription factor Arnt.
A splice variant of HIF-3, inhibitory PAS domain protein
(IPAS), inhibits the dimerization of HIF-1 and ARNT. IPAS
Figure 3. Spliced variants of HIF-3α
pre-mRNA in mice.
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