SwePub
Sök i LIBRIS databas

  Utökad sökning

WFRF:(Andreasson Anna)
 

Sökning: WFRF:(Andreasson Anna) > Licentiatavhandling > Induction of the he...

Induction of the heat-shock response by misfolded proteins

Masser, Anna E. (författare)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
Andréasson, Claes (preses)
Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut
 (creator_code:org_t)
Stockholm University, 2016
Engelska.
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Cells respond to stress by transcriptional changes intended for stress survival and adaption to further stresses. Heat shock is an intensively studied stress condition that induces in a plethora of physiological changes including increased protein misfolding. The heat-shock response (HSR) is an evolutionary conserved transcriptional response to elevated temperatures. In yeast, the HSR is governed by the transcription factors Hsf1 and Msn2/4. The HSR counteracts protein-folding stress by upregulating the expression of proteins involved in the proteostasis network including molecular chaperones and proteins involved in proteasomal degradation. Msn2/4 activity is controlled through complex signal transduction pathways involving Protein Kinase A (PKA). Hsf1 is thought to be regulated by chaperone titration, a model adapted from bacterial stress-sensing, but the mechanisms underlying its regulation are poorly understood. Here we investigate the influence that accumulated misfolded proteins have on the HSR. In study I, we evaluate a novel bioluminescent reporter system, Nanoluciferase (Nluc), for studies of the HSR in yeast. We find that codon-optimized Nluc faithfully reports on the rapid changes associated with gene induction during stress. In study II, we investigate the Hsp70 nucleotide exchange factor Fes1 and find that its nuclear splice-isoform Fes1S is involved in the degradation of misfolded proteins and a negative regulator of the HSR. In study III, we build on study II and make use of fes1Δ cells as a model for cells that have accumulated misfolded proteins. We find that accumulated misfolded proteins specifically activate Hsf1 and not Msn2/4. Interestingly, accumulated misfolded proteins potently modify both the amplitude and range of the HSR. Our findings lay the groundwork for further studies on the mechanisms that make accumulated proteins rewire cellular stress responses and Hsf1 activation.

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Nyckelord

molekylär biovetenskap
Molecular Bioscience

Publikations- och innehållstyp

vet (ämneskategori)
lic (ämneskategori)

Hitta via bibliotek

Till lärosätets databas

Hitta mer i SwePub

Av författaren/redakt...
Masser, Anna E.
Andréasson, Clae ...
Om ämnet
NATURVETENSKAP
NATURVETENSKAP
och Biologi
och Cellbiologi
Av lärosätet
Stockholms universitet

Sök utanför SwePub

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy