Prohibitin

Last updated
PHB1
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PHB1 , prohibitin, HEL-S-54e, HEL-215, PHB, prohibitin 1
External IDs OMIM: 176705; MGI: 97572; HomoloGene: 1980; GeneCards: PHB1; OMA:PHB1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002634
NM_001281496
NM_001281497
NM_001281715

NM_008831

RefSeq (protein)

NP_001268425
NP_001268426
NP_001268644
NP_002625

NP_032857

Location (UCSC) Chr 17: 49.4 – 49.41 Mb Chr 11: 95.56 – 95.57 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Prohibitin, also known as PHB, is a protein that in humans is encoded by the PHB gene. [5] 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. [6] [7]

Contents

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' untranslated region 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 androgen receptor activity and a reduction in PSA gene expression resulting in a decrease of androgen-dependent growth of prostate cancer cells. [8] 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. [5]

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. [9] The precise molecular function of the PHB complex is not clear, but a role as chaperone for respiratory 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 cell 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. [10] [11] [12] [13]

Clinical significance

Human prohibitin 1 has some activity as a virus receptor protein, having been identified as a receptor for Chikungunya Virus (CHIKV) [14] and Dengue Virus 2 (DENV-2). [15] 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

Prohibitinn in insect Prohibitin (PHB) is a highly conserved eukaryotic protein complex involved in multiple cellular processes. In insects, PHB has been identified as a potential target protein to insecticidal molecules acting as a receptor of PF2 insecticidal lectin in the midgut of Zabrotes subfasciatus larvae (bean pest) and Cry protein of Bacillus thuringiensis in Leptinotarsa decemlineata (Colorado potato beetle).

Related Research Articles

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<span class="mw-page-title-main">Androgen receptor</span> Mammalian protein found in humans

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<span class="mw-page-title-main">PELP-1</span> Mammalian protein found in Homo sapiens

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<span class="mw-page-title-main">Estrogen receptor alpha</span> Protein-coding gene in the species Homo sapiens

Estrogen receptor alpha (ERα), also known as NR3A1, is one of two main types of estrogen receptor, a nuclear receptor that is activated by the sex hormone estrogen. In humans, ERα is encoded by the gene ESR1.

The ERRs are orphan nuclear receptors, meaning the identity of their endogenous ligand has yet to be unambiguously determined. They are named because of sequence homology with estrogen receptors, but do not appear to bind estrogens or other tested steroid hormones.

<span class="mw-page-title-main">HDAC1</span> Protein-coding gene in the species Homo sapiens

Histone deacetylase 1 (HDAC1) is an enzyme that in humans is encoded by the HDAC1 gene.

<span class="mw-page-title-main">Small heterodimer partner</span> Protein found in humans

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<span class="mw-page-title-main">E2F1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">NRIP1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PA2G4</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Estrogen-related receptor alpha</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Testicular receptor 2</span> Human protein-coding gene

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<span class="mw-page-title-main">Testicular receptor 4</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PIAS3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">PHB2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">FOXA1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">SRARP</span> Protein-coding gene in the species Homo sapiens

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000167085 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000038845 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Gene: PHB prohibitin".
  6. Van Aken O, Pecenková T, van de Cotte B, De Rycke R, Eeckhout D, Fromm H, De Jaeger G, Witters E, Beemster GT, Inzé D, Van Breusegem F (Dec 2007). "Mitochondrial type-I prohibitins of Arabidopsis thaliana are required for supporting proficient meristem development". The Plant Journal. 52 (5): 850–64. doi: 10.1111/j.1365-313X.2007.03276.x . PMID   17883375.
  7. Mishra S, Murphy LC, Murphy LJ (2006). "The Prohibitins: emerging roles in diverse functions". Journal of Cellular and Molecular Medicine. 10 (2): 353–63. doi:10.1111/j.1582-4934.2006.tb00404.x. PMC   3933126 . PMID   16796804.
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  9. Tatsuta T, Model K, Langer T (Jan 2005). "Formation of membrane-bound ring complexes by prohibitins in mitochondria". Molecular Biology of the Cell. 16 (1): 248–59. doi:10.1091/mbc.E04-09-0807. PMC   539169 . PMID   15525670.
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  24. Pérez-Perarnau A, Preciado S, Palmeri CM, Moncunill-Massaguer C, Iglesias-Serret D, González-Gironès DM, Miguel M, Karasawa S, Sakamoto S, Cosialls AM, Rubio-Patiño C, Saura-Esteller J, Ramón R, Caja L, Fabregat I, Pons G, Handa H, Albericio F, Gil J, Lavilla R (Sep 2014). "A trifluorinated thiazoline scaffold leading to pro-apoptotic agents targeting prohibitins". Angewandte Chemie. 53 (38): 10150–4. doi:10.1002/anie.201405758. PMID   25196378.
  25. Moncunill-Massaguer C, Saura-Esteller J, Pérez-Perarnau A, Palmeri CM, Núñez-Vázquez S, Cosialls AM, González-Gironès DM, Pomares H, Korwitz A, Preciado S, Albericio F, Lavilla R, Pons G, Langer T, Iglesias-Serret D, Gil J (Dec 2015). "A novel prohibitin-binding compound induces the mitochondrial apoptotic pathway through NOXA and BIM upregulation". Oncotarget. 6 (39): 41750–65. doi:10.18632/oncotarget.6154. PMC   4747186 . PMID   26497683.
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Further reading