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Sse2p, renders cells slow-growing, which is exacerbated by temperature stress (Liu
et al.
1999
). Overexpression of Sse1p also results in a slow-growth phenotype. The
simultaneous deletion of both genes is lethal (Raviol et al.
2006b
). Over-expres-
sion of the HspBP1 homolog Fes1p can partially compensate
sse1,2
Δ (Raviol et al.
2006b
). Sse1p collaborates with both forms of cytosolic Hsp70, Ssa1-4 and the
ribosome-associated Ssb1/2 to fold newly synthesized proteins (Yam et al.
2005
;
Shaner et al.
2005
). This is dependent on the ribosome-associated complex (RAC)
(Koplin et al.
2010
; Willmund et al.
2013
), containing the J-protein Zuo1p, and
the type-I J-domain protein Ydj1p, respectively (Shaner et al.
2006
). Interactions
of Sse1p with 1940 potential substrate proteins were listed in a proteomics survey
(Gong et al.
2009
), a substantial part of the yeast proteome (~ 6600 proteins). Sse1p
function also appears to have an impact on Hsp90 client proteins such as kinases
and nuclear receptors (Goeckeler et al.
2002
; Liu et al.
1999
), probably by upstream
client processing through the Hsp70 system. Specific examples are the growth con-
trol kinase Sch9p (Trott et al.
2005
) and the MAP kinase Slt2p (Shaner et al.
2008
),
enabling Slt2p interaction with downstream effectors required for yeast cell wall
integrity and morphogenesis. The NEF-function of Sse1p for Ssa1/2 is required
for proper distribution of the kinesin-5 motor during bipolar spindle assembly, thus
preventing premature spindle elongation during mitosis (Makhnevych et al.
2012
).
Besides de novo protein folding, Sse1p is also deeply involved in cellular protein
quality control, as shown by the impact of its absence on the proteasomal clearance
of the von-Hippel-Lindau (VHL) tumor suppressor protein (McClellan et al.
2005
),
a model substrate for the chaperonin TRiC, which cannot stably fold in absence
of its complex partners Elongin-BC, and a folding-defective mutant version of the
Hsp90 client protein Ste11p (Mandal et al.
2010
).
The cellular concentration of Fes1p, the yeast homolog of HspBP1, is ~5-fold
lower than Sse1p, and its expression is up-regulated upon stress. Fes1p catalyzes
nucleotide exchange both on Ssa and Ssb-type Hsp70 proteins (Dragovic et al.
2006b
; Kabani et al.
2002a
) and associates with translating ribosomes (Kabani
et al.
2002a
). Fes1p and RAC appear to compete for binding to Ssb Hsp70 proteins,
perhaps indicating the necessity for sequential interactions—RAC and Ssb⋅AT P
upon emergence of the nascent chain at the ribosomal exit channel and Fes1p and
Ssb⋅ADP towards completion of translation (Dragovic et al.
2006b
). Deletion of
FES1
causes a growth defect under heat stress and a folding defect in the reporter
protein firefly luciferase (FLuc) (Ahner et al.
2005
; Shomura et al.
2005
). Binding
to Hsp70 and nucleotide exchange activity are critical for Fes1p function, since the
inactive, but structurally intact mutant Fes1p(A79R/R195A) cannot complement
the phenotype (Shomura et al.
2005
). Deletion of
FES1
induces a massive heat
shock response with strong up-regulation of molecular chaperones under standard
growth conditions, while
sse1
Δ triggers only a mild induction, suggesting a criti-
cal function of Fes1p in the heat shock factor (Hsf1) activation pathway (Abrams
et al.
2014
; Gowda et al.
2013
). This might explain why the growth defect of
fes1
Δ
is relatively mild compared to the latter strain. Interestingly, Fes1p was implicated
in the proteasome-mediated clearance of the constitutively misfolded proteins DH-
FRmutC, DHFRmutD and the protein fragment Rpo41(T920-L1217), but not in the
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