Gli3
Encyclopedia
Zinc finger protein GLI3 is a protein
that in humans is encoded by the GLI3 gene
.
This gene encodes a protein
that belongs to the C2H2-type zinc finger
proteins subclass of the Gli family. They are characterized as DNA-binding transcription factor
s and are mediators of Sonic hedgehog
(Shh) signaling
. The protein encoded by this gene localizes in the cytoplasm
and activates patched Drosophila homolog (PTCH1
) gene expression. It is also thought to play a role during embryogenesis
.
repressor
but may also have a positive transcriptional function. Gli3 represses dHand
and Gremlin
, which are involved in developing digit
s. There is evidence that Shh
-controlled processing (e.g., cleavage) regulates transcriptional activity of Gli3 similarly to that of CI
. Gli3 mutant mice have many abnormalities including CNS
and lung
defects and limb polydactyly
.
There is evidence that the autosomal
dominant disorder Greig cephalopolysyndactyly syndrome
(GCPS) that affects limb and craniofacial development in human
s is caused by a translocations within the GLI3 gene.
and Gli2
in mice
models to lead to formation of basal cell carcinoma
(BCC). Gli1 knockout is shown to lead to similar embryo
nic malformations as Gli1 overexpressions but not the formation of BCCs. Overexpression of Gli3 in transgenic mice and frogs does not lead to the development of BCC-like tumors and is not thought to play a role in tumor
BCC formation.
Gli1 and Gli2 overexpression leads to BCC formation in mouse models and a one step model for tumour formation has been suggested in both cases. This also indicates that Gli1 and/or Gli2 overexpression is vital in BCC formation. Co-overexpression of Gli1 with Gli2 and Gli2 with Gli3 leads to transgenic mice malformations and death, respectively, but not the formation of BCC. This suggests that overexpression of more than one Gli protein
is not necessary for BCC formation.
with CREBBP SUFU
, ZIC1
, and ZIC2
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the GLI3 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
This gene encodes a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that belongs to the C2H2-type zinc finger
Zinc finger
Zinc fingers are small protein structural motifs that can coordinate one or more zinc ions to help stabilize their folds. They can be classified into several different structural families and typically function as interaction modules that bind DNA, RNA, proteins, or small molecules...
proteins subclass of the Gli family. They are characterized as DNA-binding 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 and are mediators of Sonic hedgehog
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
(Shh) signaling
Hedgehog signaling pathway
In a growing embryo, cells develop differently in the head or tail end of the embryo, the left or right, and other positions. They also form segments which develop into different body parts. The hedgehog signaling pathway gives cells information that they need to make the embryo develop properly....
. The protein encoded by this gene localizes in the cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
and activates patched Drosophila homolog (PTCH1
PTCH1
Protein patched homolog 1 is a protein that is the member of the Patched family and in humans is encoded by the PTCH1 gene.- Function :PTCH1 is a member of the patched gene family and is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in...
) gene expression. It is also thought to play a role during embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
.
Role in development
Gli3 is a known transcriptionalTranscription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
repressor
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
but may also have a positive transcriptional function. Gli3 represses dHand
HAND2
Heart- and neural crest derivatives-expressed protein 2 is a protein that in humans is encoded by the HAND2 gene.A progesterone-regulated transcription factor regulates stromal-epithelial communication in early pregnancy....
and Gremlin
FIGLA
Folliculogenesis-specific basic helix-loop-helix, also known as factor in the germline alpha or transcription factor FIGa, is a protein that in humans is encoded by the FIGLA gene.- Function :...
, which are involved in developing digit
Toe
Toes are the digits of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being digitigrade. Humans, and other animals that walk on the soles of their feet, are described as being plantigrade; unguligrade animals are those that walk on hooves at the tips of...
s. There is evidence that Shh
SHH
SHH can refer to:* Summer Heights High, an Australian TV series* Sonic hedgehog, an important protein during vertebrate organogenesis* Students Helping Honduras, an international non-governmental organization operating in the U.S. and Honduras...
-controlled processing (e.g., cleavage) regulates transcriptional activity of Gli3 similarly to that of CI
CI protein
cI protein , also known as the lambda repressor, is the sole protein expressed in the lysogenic state of Lambda phage. cI turns off transcription at the phage's L and R promoters as well as any other invading lambda phages into the host cell. It is a transcription factor and contains the common...
. Gli3 mutant mice have many abnormalities including CNS
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
and lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
defects and limb polydactyly
Polydactyly
Polydactyly or polydactylism , also known as hyperdactyly, is a congenital physical anomaly in humans, dogs, and cats having supernumerary fingers or toes....
.
Disease association
Mutations in this gene have been associated with several diseases, including Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, and postaxial polydactyly types A1 and B.There is evidence that the autosomal
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
dominant disorder Greig cephalopolysyndactyly syndrome
Greig cephalopolysyndactyly syndrome
Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe...
(GCPS) that affects limb and craniofacial development in human
Human
Humans are the only living species in the Homo genus...
s is caused by a translocations within the GLI3 gene.
Interactions with Gli1 and Gli2
The independent overexpression Gli1Gli1
Gli1 is a protein originally isolated in human glioblastoma.-Overview:The Gli proteins are the effectors of Hedgehog signaling and have been shown to be involved in cell fate determination, proliferation and patterning in many cell types and most organs during embryo development.The Gli...
and Gli2
Gli2
Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene. The protein encoded by this gene is a transcription factor....
in mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...
models to lead to formation of basal cell carcinoma
Basal cell carcinoma
Basal-cell carcinoma is the most common type of skin cancer. It rarely metastasizes or kills. However, because it can cause significant destruction and disfigurement by invading surrounding tissues, it is still considered malignant. Statistically, approximately 3 out of 10 Caucasians may develop a...
(BCC). Gli1 knockout is shown to lead to similar embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
nic malformations as Gli1 overexpressions but not the formation of BCCs. Overexpression of Gli3 in transgenic mice and frogs does not lead to the development of BCC-like tumors and is not thought to play a role in tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
BCC formation.
Gli1 and Gli2 overexpression leads to BCC formation in mouse models and a one step model for tumour formation has been suggested in both cases. This also indicates that Gli1 and/or Gli2 overexpression is vital in BCC formation. Co-overexpression of Gli1 with Gli2 and Gli2 with Gli3 leads to transgenic mice malformations and death, respectively, but not the formation of BCC. This suggests that overexpression of more than one Gli protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
is not necessary for BCC formation.
Interactions
GLI3 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with CREBBP SUFU
SUFU
Suppressor of fused homolog is a protein that in humans is encoded by the SUFU gene.- Function :SUFU encodes a component of the sonic hedgehog / patched signaling pathway...
, ZIC1
ZIC1
Zinc finger protein ZIC 1 is a protein that in humans is encoded by the ZIC1 gene.-Interactions:ZIC1 has been shown to interact with GLI1 and GLI3.-Further reading:...
, and ZIC2
ZIC2
Zinc finger protein ZIC 2 is a protein that in humans is encoded by the ZIC2 gene.-Further reading:...
.