In
molecular biology
Molecular biology is a branch of biology that seeks to understand the molecule, molecular basis of biological activity in and between Cell (biology), cells, including biomolecule, biomolecular synthesis, modification, mechanisms, and interactio ...
, heat shock factors (HSF), are the
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s that regulate the expression of the
heat shock proteins.
A typical example is the heat shock factor of ''
Drosophila melanogaster
''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...
''.
Function
Heat shock factors (HSF) are transcriptional activators of heat shock genes.
These activators bind specifically to Heat Shock sequence Elements (HSE) throughout the genome
whose consensus-sequence is a tandem array of three oppositely oriented "AGAAN" motifs or a degenerate version thereof. Under non-stressed conditions, Drosophila HSF is a nuclear-localized unbound monomer, whereas heat shock activation results in
trimerization and binding to the HSE.
The Heat Shock sequence Element is highly conserved from yeast to humans.
Heat shock factor 1 (HSF-1) is the major regulator of heat shock protein transcription in
eukaryote
The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s. In the absence of cellular stress, HSF-1 is inhibited by association with heat shock proteins and is therefore not active. Cellular stresses, such as increased temperature, can cause proteins in the cell to misfold. Heat shock proteins bind to the misfolded proteins and dissociate from HSF-1. This allows HSF1 to form trimers and translocate to the
cell nucleus
The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...
and activate transcription.
Its function is not only critical to overcome the proteotoxic effects of thermal stress, but also needed for proper animal development and the overall survival of cancer cells.
Structure
Each HSF monomer contains one
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
and three
N-terminal leucine zipper
A leucine zipper (or leucine scissors) is a common three-dimensional structural motif in proteins. They were first described by Landschulz and collaborators in 1988 when they found that an enhancer binding protein had a very characteristic 30-amin ...
repeats.
Point mutations in these regions result in disruption of cellular localisation, rendering the protein constitutively nuclear in humans.
Two sequences flanking the N-terminal zippers fit the consensus of a bi-partite
nuclear localization signal
A nuclear localization signal ''or'' sequence (NLS) is an amino acid sequence that 'tags' a protein for import into the cell nucleus by nuclear transport. Typically, this signal consists of one or more short sequences of positively charged lysin ...
(NLS). Interaction between the N- and C-terminal zippers may result in a structure that masks the NLS sequences: following activation of HSF, these may then be unmasked, resulting in relocalisation of the protein to the nucleus.
The DNA-binding component of HSF lies to the N-terminus of the first NLS region, and is referred to as the HSF domain.
Isoforms
Humans express the following heat shock factors:
See also
*
Cold-shock domain
References
{{Transcription factors, g3
Transcription factors