Preferred Label : HSP27 Regulation Pathway;
NCIt related terms : Stress Induction of HSP Regulation;
Alternative definition : BIOCARTA: Mammalian cells can respond to a variety of stresses such as heat, cold,
oxidative stress, metabolic disturbance, and environmental toxins through necrotic
or apoptotic cell death, while increased expression and phosphorylation of heat shock
proteins such as Hsp27 can protect cells against cellular stress. Heat shock proteins
commonly exhibit molecular chaperone activity and also interact with a wide variety
of proteins to exert specific effects. The small heat shock protein Hsp27 exists as
monomers, dimers, and oligomers in the cell, and each form has distinct activities.
Oligomers are the main form of Hsp27 with molecular chaperone activity and are disrupted
by phosphorylation of Hsp27 to form dimers and monomers. S-thiolation of Hsp27 on
cysteine also dissociates oligomers and may provide another route of regulating the
action of Hsp27 in stress. Map kinase cascades mediate Hsp27 phosphorylation. Heat
stress activates the p38 kinase cascade and induces phosphorylation of Hsp27 by the
downstream Map kinases Mapkapk2 and Mapkap3. Cytokines such as TNF and IL-1 can also
induce Hsp27 phosphorylation through this Map kinase cascade, protecting cells in
some settings against cytotoxic responses. In stressful conditions, dissociation of
oligomeric Hsp27 by phosphorylation may allow lower molecular weight forms to perform
other non-chaperone functions. One action of Hsp27 induced by stress is to protect
cells against apoptosis and a common component of apoptotic pathways is the mitochondrial
release of cytochrome c. One way that Hsp27 reduces apoptosis is by preventing the
release of cytochrome c and by binding to cytochrome c in the cytosol. Downstream,
Hsp27 also blocks caspase 9 activation and the subsequent activation of caspase 3,
inhibiting the rest of the proteolytic caspase cascade. Yet a further role of Hsp27
in blocking apoptosis is through blocking Fas-induced apoptosis. Fas is a receptor
in the TNF receptor gene family that induces apoptosis when stimulated by its cell-bound
ligand, Fas-ligand. Fas induces apoptosis through two pathways, one mediated by the
protein Daxx. Phosphorylated Hsp27 dimers block apoptosis by binding with Daxx and
preventing downstream activation of the kinase Ask1. The interaction of Hsp27 with
actin filaments may also prevent apoptosis triggered by some agents like staurosporine
that damage actin. Unphosphorylated Hsp27 monomers regulate actin filament growth
by binding to the end of fibers and capping them. Finally, Hsp27 appears to prevent
damage to cells by reactive oxygen species (ROS), by altering the oxidative environment
of the cell through induction of glutathione expression, as well as blocking apoptosis
induced by ROS. Modulation of Hsp27 expression and phosphorylation may provide a useful
means to alter cellular sensitivity to stress. (This definition may be outdated -
see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_hsp27Pathway;
Origin ID : C39108;
UMLS CUI : C1512322;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
