Heat shock factor in molecular biology

Molecular biology

Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

, is the name given to transcription factor

Transcription factor

In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...

s that regulate the expression of the heat shock proteins. A typical example is the heat shock factor of Drosophila melanogaster

Drosophila melanogaster

Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

.

Function

Heat shock factors (HSF) are transcriptional activators of heat shock genes. They bind specifically to heat shock promoter elements, which are palindromic

Palindrome

A palindrome is a word, phrase, number, or other sequence of units that can be read the same way in either direction, with general allowances for adjustments to punctuation and word dividers....

 sequences rich with repetitive purine

Purine

A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....

 and pyrimidine

Pyrimidine

Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...

 motifs. Under normal conditions, HSF is a homo-trimeric cytoplasmic protein, but heat shock activation results in relocalisation to the nucleus.

Heat shock factor 1 (HSF-1) is the major regulator of heat shock protein transcription in eukaryotes

Eukaryote

A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

. 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

Cell nucleus

In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...

 and activate transcription.

Structure

Each HSF monomer contains one C-terminal and three N-terminal leucine zipper

Leucine zipper

A leucine zipper, aka leucine scissors, is a common three-dimensional structural motif in proteins. These motifs are usually found as part of a DNA-binding domain in various transcription factors, and are therefore involved in regulating gene expression...

 repeats. Point mutations in these regions result in disruption of cellular localisation, rendering the protein constitutively nuclear. Two sequences flanking the N-terminal zippers fit the consensus of a bi-partite nuclear localization signal

Nuclear localization signal

A nuclear localization signal or sequence is an amino acid sequence which '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 lysines or arginines exposed on the protein surface. Different...

 (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:

gene	protein
HSF1 HSF1 Heat shock factor protein 1 is a protein that in humans is encoded by the HSF1 gene.-Function:The product of this gene is a heat-shock transcription factor. Transcription of heat-shock genes is rapidly induced after temperature stress...	heat shock transcription factor 1
HSF2 HSF2 Heat shock factor protein 2 is a protein that in humans is encoded by the HSF2 gene.-Interactions:HSF2 has been shown to interact with Nucleoporin 62 and HSF1....	heat shock transcription factor 2
	heat shock transcription factor 2 binding protein
HSF4 HSF4 Heat shock factor protein 4 is a protein that in humans is encoded by the HSF4 gene....	heat shock transcription factor 4
	heat shock transcription factor family member 5
	heat shock transcription factor family, X linked 1
	heat shock transcription factor family, X linked 2
	heat shock transcription factor, Y-linked 1
	heat shock transcription factor, Y-linked 2