Prohibitin

PHB
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1LU7
Identifiers
Aliases	PHB, HEL-215, HEL-S-54e, PHB1, prohibitin
External IDs	MGI: 97572 HomoloGene: 1980 GeneCards: PHB
Gene ontology Molecular function • histone deacetylase binding • complement component C3a binding • protein C-terminus binding • proteinase activated receptor binding • complement component C3b binding • protein binding • enzyme binding • transcription regulatory region DNA binding • RNA polymerase II transcription factor activity, sequence-specific DNA binding Cellular component • cytoplasm • membrane • myelin sheath • plasma membrane • integral component of plasma membrane • nucleoplasm • cell surface • early endosome • mitochondrion • mitochondrial inner membrane • extracellular exosome • nucleus Biological process • regulation of apoptotic process • negative regulation of glucocorticoid receptor signaling pathway • DNA biosynthetic process • regulation of transcription, DNA-templated • cellular response to interleukin-6 • negative regulation of protein catabolic process • negative regulation of transcription by competitive promoter binding • protein stabilization • negative regulation of androgen receptor signaling pathway • mitochondrion organization • negative regulation of transcription from RNA polymerase II promoter • positive regulation of transcription, DNA-templated • positive regulation of G-protein coupled receptor protein signaling pathway • negative regulation of cell growth • osteoblast differentiation • positive regulation of ERK1 and ERK2 cascade • positive regulation of complement activation • negative regulation of ERK1 and ERK2 cascade • progesterone receptor signaling pathway • negative regulation of transcription, DNA-templated • histone deacetylation • signal transduction • negative regulation of cell proliferation • positive regulation of gene expression • positive regulation of cell death Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5245	18673
Ensembl	ENSG00000167085	ENSMUSG00000038845
UniProt	P35232	P67778
RefSeq (mRNA)	NM_002634 NM_001281496 NM_001281497 NM_001281715	NM_008831
RefSeq (protein)	NP_001268425.1 NP_001268426.1 NP_001268644.1 NP_002625.1	NP_032857.1
Location (UCSC)	Chr 17: 49.4 – 49.41 Mb	Chr 11: 95.67 – 95.68 Mb
PubMed search	[1]	[2]
Wikidata

Prohibitin, also known as PHB, is a protein that in humans is encoded by the PHB gene.^[3] 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.^[4][5]

Discovery

Prohibitins are evolutionarily conserved genes that are ubiquitously expressed. The human prohibitin gene, located on the BRCA1 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. However, over-expression of PHB has been associated with a reduction in the androgen receptor activity and a reduction in PSA gene expression resulting in a decrease of androgen-dependent growth of cancerous prostate cells.^[6] 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.^[3]

Function

Prohibitins may have multiple functions including:

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.^[7] 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 transcriptional activity by interacting with various transcription factors, including nuclear receptors, 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.^{[8][9][10][11]}

Clinical significance

Human prohibitin 1 has some activity as a virus receptor protein, having been identified as a receptor for Chikungunya Virus (CHIKV)^[12] and Dengue Virus 2 (DENV-2).^[13] Little else is known about the activity of the prohibitins in viral pathogenesis.

Interactions

Prohibitin has been shown to interact with:

Drugs that bind to prohibitin

• Aurilide ^[21]
• Fluorizoline ^[22][23]
• Rocaglamide A ^[24]

References

Further reading