Prohibitin
Encyclopedia
Prohibitin, also known as PHB, is a protein
that in humans is encoded by the PHB gene
.
The Phb gene has also been described in animals, fungi, plants, and unicellular eukaryotes. Prohibitins are divided in two classes, termed Type-I and Type-II prohibitins, based on their similarity to yeast PHB1 and PHB2, respectively. Each organism has at least one copy of each type of prohibitin gene.
chromosome region 17q21, was originally thought to be a negative regulator of cell proliferation and a tumor suppressor. This anti-proliferative activity was later attributed to the 3' UTR of the PHB gene, and not to the actual protein. Mutations in human PHB have been linked to sporadic breast cancer. Prohibitin is expressed as two transcripts with varying lengths of 3' untranslated region. The longer transcript is present at higher levels in proliferating tissues and cells, suggesting that this longer 3' untranslated region may function as a trans-acting regulatory RNA.
activity by interacting with various transcription factor
s, including nuclear receptor
s, either directly or indirectly. However, little evidence for nuclear targeting and transcription factor-binding of prohibitins has been found in other organism (yeast, plants, C. elegans, etc.), indicating that this may be a specific function in mammalian cells.
with HDAC1
, C-Raf
, Retinoblastoma-like protein 2
, Retinoblastoma-like protein 1
, E2F1
, SMARCA2
, Retinoblastoma protein
, P53
, Annexin A2
and SMARCA4
.
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 PHB 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...
.
The Phb gene has also been described in animals, fungi, plants, and unicellular eukaryotes. Prohibitins are divided in two classes, termed Type-I and Type-II prohibitins, based on their similarity to yeast PHB1 and PHB2, respectively. Each organism has at least one copy of each type of prohibitin gene.
Discovery
Prohibitins are evolutionarily conserved genes that are ubiquitously expressed. The human prohibitin gene, located on the BRCA1BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...
chromosome region 17q21, was originally thought to be a negative regulator of cell proliferation and a tumor suppressor. This anti-proliferative activity was later attributed to the 3' UTR of the PHB gene, and not to the actual protein. Mutations in human PHB have been linked to sporadic breast cancer. Prohibitin is expressed as two transcripts with varying lengths of 3' untranslated region. The longer transcript is present at higher levels in proliferating tissues and cells, suggesting that this longer 3' untranslated region may function as a trans-acting regulatory RNA.
Mitochondrial function and morphology
Prohibitins are assembled into a ring-like structure with 16–20 alternating Phb1 and Phb2 subunits in the inner mitochondrial membrane. The precise molecular function of the PHB complex is not clear, but a role as chaperone for respiration chain proteins or as a general structuring scaffold required for optimal mitochondrial morphology and function are suspected. Recently, prohibitins have been demonstrated to be positive, rather than negative, regulators of cell proliferation in both plants and mice.Transcriptional modulation
Both human prohibitins have also been suggested to be localized in the nucleus and modulate 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...
activity by interacting with various 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, including nuclear receptor
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
s, either directly or indirectly. However, little evidence for nuclear targeting and transcription factor-binding of prohibitins has been found in other organism (yeast, plants, C. elegans, etc.), indicating that this may be a specific function in mammalian cells.
Interactions
Prohibitin 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 HDAC1
HDAC1
Histone deacetylase 1 is an enzyme that in humans is encoded by the HDAC1 gene.-Interactions:HDAC1 has been shown to interact with RAD9A, DNMT3L, MTA1, FKBP3, CDC20, CDH1, Host cell factor C1, BUB3, Nuclear receptor co-repressor 2, IKZF1, Prohibitin, EVI1, DDX5, DNMT3A, Mothers against...
, C-Raf
C-Raf
RAF proto-oncogene serine/threonine-protein kinase also known as proto-oncogene c-RAF or simply c-Raf is an enzyme that in humans is encoded by the RAF1 gene. The c-Raf protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade...
, Retinoblastoma-like protein 2
Retinoblastoma-like protein 2
Retinoblastoma-like protein 2 is a protein that in humans is encoded by the RBL2 gene.-Interactions:Retinoblastoma-like protein 2 has been shown to interact with HDAC1, C-Raf, RBBP8, Cyclin E1, Prohibitin, Cyclin-dependent kinase 2, BRF1 and BRCA1....
, Retinoblastoma-like protein 1
Retinoblastoma-like protein 1
Retinoblastoma-like 1 , also known as RBL1, is a protein that in humans is encoded by the RBL1 gene.- Function :The protein encoded by this gene is similar in sequence and possibly function to the product of the retinoblastoma 1 gene...
, E2F1
E2F1
Transcription factor E2F1 is a protein that in humans is encoded by the E2F1 gene.-Interactions:E2F1 has been shown to interact with NCOA6, Retinoblastoma-like protein 1, Retinoblastoma protein, GTF2H1, SKP2, PURA, NPDC1, Sp2 transcription factor, Sp1 transcription factor, CUL1, ARID3A, TOPBP1,...
, SMARCA2
SMARCA2
Probable global transcription activator SNF2L2 is a protein that in humans is encoded by the SMARCA2 gene.-Interactions:SMARCA2 has been shown to interact with SS18, ACTL6A, SIN3A, POLR2A, Prohibitin, SMARCC1, CEBPB, SMARCB1 and ARID1B....
, Retinoblastoma protein
Retinoblastoma protein
The retinoblastoma protein is a tumor suppressor protein that is dysfunctional in the majority types of cancer. One highly studied function of pRb is to prevent excessive cell growth by inhibiting cell cycle progression until a cell is ready to divide...
, P53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
, Annexin A2
Annexin A2
Annexin A2 also known as annexin II is a protein that in humans is encoded by the ANXA2 gene.Annexin 2 is involved in diverse cellular processes such as cell motility , linkage of membrane-associated protein complexes to the actin cytoskeleton, endocytosis, fibrinolysis, ion channel formation, and...
and SMARCA4
SMARCA4
Transcription activator BRG1 also known as ATP-dependent helicase SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.- Function :...
.