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Printable Handouts
Navigable Slide Index
- Introduction
- Heat shock genes and proteins discovery
- Heat shock elements and transcription factor 1
- Conditions for activation of HSF-1
- 5 different heat shock protein families
- Some families are nor HSF-1 regulated
- HSPs are molecular chaperones
- HSPs and folding of nascent proteins
- Heat-induced HSP up-regulation
- HSP70 and toxicity protection
- HSPs and mutant proteins
- HSPs: expansion and functional diversification
- Interaction between different HSP families
- HSP70 machines
- Functional specificity via different HSP70s
- Functional specificity via different NEFs
- Functional specificity via different DNAJs
- Functional classification of DNAJ proteins
- Promiscuous client binding in DNAJ proteins
- Ydj1 and Sis1/DNAJB1 generally promote refolding
- DNAJB2 directs clients to degradation
- Selective client binding
- DNAJs without client binding for tethering HSP70
- DNAJC2
- Functional specificity beyond DNAJs
- The HSP70 machine and folding diseases
- PolyQ diseases
- Recognizing HSPs in polyQ disease
- DNAJB6/8 suppressors of poly-Q aggregation
- DNAJB6/8 protect against poly-Q toxicity
- Deletion of SSF-SST region of DNAJB8
- DNAJB6 / DNAJB8 interact with HDACs
- HDAC4 is required for DNAJB6/8 function
- DNAJB8 acetylation
- C-terminal lysines involved in activity of DNAJB8
- DNAJB6 prevents polyQ aggregation in vitro
- DNAJB6/8 prevent polyQ aggregation in cells
- A model of prevention of polyQ aggregation
- HSPB expansion and functional diversification
- HSPB alpha-crystalline domain
- Human HSPB family
- Refolding vs. polyQ aggregation
- Canonical mechanism of refolding
- Non-canonical mechanism of refolding
- Summary
- Acknowledgements
- References
Topics Covered
- Heat shock proteins
- Regulation and chaperone activity
- Several protein families with many different members
- DNAJ family
- Regulation of differentiation of HSP machines to drive client specificity and differential client processing
- Involvement in folding, proteasomal degradation, autophagy
- Potent suppressors of protein deposit diseases, e.g. CAG repeat diseases
Talk Citation
Kampinga, H. (2012, February 2). Human heat shock protein families [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 27, 2024, from https://doi.org/10.69645/YGYV2916.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Herman Kampinga has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Biochemistry
Transcript
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0:00
Welcome to this webinar
on human heat shock
protein families.
My name is Harm Kampinga.
I'm a member of the
Department of Cell Biology at
the University Medical Center
in Groningen, the Netherlands.
In this webinar, I will discuss
with you the functional
diversity of
these human heat shock
protein families
and their relevance
to human diseases.
First, I will show you
how heat shock proteins
were discovered.
Next, I will introduce
the basic concepts
of chaperone action.
Thereafter, the various
human heat shock protein
families will be introduced,
and I will go into
the functionality
of the HSP70 machines,
and how they're regulated in
terms of functional
differentiation,
especially by DNAJ proteins.
These HSP70 DNAJ combinations
will next be discussed in terms
of their relevance
to folding diseases.
Finally, I will discuss a bit on
the small heat shock
protein families
or HSPB families in humans,
how they've expanded,
and how these proteins have
various functions also in
human protein folding diseases,
some with links to the
process of autophagy.
1:13
Originally heat shock genes were
discovered already
in 1962 by Ritossa.
Studying gene expression using
the giant chromosomes in
the slivery gland
tissue from drosophila,
he found a complete
ambrein pattern
at a certain moment in his lab.
When he looked back
at his incubator,
he found that his incubator
had been at too
high a temperature.
He repeated the
experiment and found that
this puffing pattern really
was induced by a heat shock.
In fact, most other patterns
were completely
repressed whereas
these particular new
genes that he called
heat shock genes were expressed
at higher temperatures
preferentially.
In this slide, you can see
the original data from
Ritossa in which the
upper panel represents
the normal control
chromosomes and
the lower panel chromosomes
after the cells had been
exposed to this heat shock.
It took another 12
years before Tissieres
discovered that these were
in fact then also
translated into proteins.
This discovery was made
two years after Laemmli
had developed his SDS-PAGE
gel electrophoresis.
In the lower image, you find
the original gels of heat here.
What you can see here is
an autoradiogram of cells
exposed to a heat shock and you
see the specific profile of
heat shock proteins being
induced upon this
particular heat shock.
This is how these proteins got
their name and they were
originally described to
be genes or proteins of which
the expression was increased
after a heat shock.