8rrh

Structural highlights

Function

PHB1_HUMAN Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors in the nucleus (PubMed:11302691, PubMed:20959514, PubMed:28017329, PubMed:31522117). Plays a role in adipose tissue and glucose homeostasis in a sex-specific manner (By similarity). Contributes to pulmonary vascular remodeling by accelerating proliferation of pulmonary arterial smooth muscle cells (By similarity).[UniProtKB:P67778][UniProtKB:P67779]^{[1] [2] [3] [4]} In the mitochondria, together with PHB2, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan (Probable). The prohibitin complex, with DNAJC19, regulates cardiolipin remodeling and the protein turnover of OMA1 in a cardiolipin-binding manner (By similarity). Regulates mitochondrial respiration activity playing a role in cellular aging (PubMed:11302691). The prohibitin complex plays a role of mitophagy receptor involved in targeting mitochondria for autophagic degradation (PubMed:28017329). Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and pro-inflammatory cytokine IL6 (PubMed:31522117).[UniProtKB:P67778]^{[5] [6] [7]} In the nucleus, acts as a transcription coregulator, enhances promoter binding by TP53, a transcription factor it activates, but reduces the promoter binding by E2F1, a transcription factor it represses (PubMed:14500729). Interacts with STAT3 to affect IL17 secretion in T-helper Th17 cells (PubMed:31899195).^{[8] [9]} In the plasma membrane, cooperates with CD86 to mediate CD86-signaling in B lymphocytes that regulates the level of IgG1 produced through the activation of distal signaling intermediates (By similarity). Upon CD40 engagement, required to activate NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity).[UniProtKB:P67778]

References

1. ↑ Coates PJ, Nenutil R, McGregor A, Picksley SM, Crouch DH, Hall PA, Wright EG. Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. Exp Cell Res. 2001 May 1;265(2):262-73. PMID:11302691 doi:10.1006/excr.2001.5166
2. ↑ Strub GM, Paillard M, Liang J, Gomez L, Allegood JC, Hait NC, Maceyka M, Price MM, Chen Q, Simpson DC, Kordula T, Milstien S, Lesnefsky EJ, Spiegel S. Sphingosine-1-phosphate produced by sphingosine kinase 2 in mitochondria interacts with prohibitin 2 to regulate complex IV assembly and respiration. FASEB J. 2011 Feb;25(2):600-12. PMID:20959514 doi:10.1096/fj.10-167502
3. ↑ Wei Y, Chiang WC, Sumpter R Jr, Mishra P, Levine B. Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor. Cell. 2017 Jan 12;168(1-2):224-238.e10. PMID:28017329 doi:10.1016/j.cell.2016.11.042
4. ↑ Yoshinaka T, Kosako H, Yoshizumi T, Furukawa R, Hirano Y, Kuge O, Tamada T, Koshiba T. Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region. iScience. 2019 Sep 27;19:1065-1078. doi: 10.1016/j.isci.2019.08.056. Epub 2019, Sep 3. PMID:31522117 doi:http://dx.doi.org/10.1016/j.isci.2019.08.056
5. ↑ Coates PJ, Nenutil R, McGregor A, Picksley SM, Crouch DH, Hall PA, Wright EG. Mammalian prohibitin proteins respond to mitochondrial stress and decrease during cellular senescence. Exp Cell Res. 2001 May 1;265(2):262-73. PMID:11302691 doi:10.1006/excr.2001.5166
6. ↑ Wei Y, Chiang WC, Sumpter R Jr, Mishra P, Levine B. Prohibitin 2 Is an Inner Mitochondrial Membrane Mitophagy Receptor. Cell. 2017 Jan 12;168(1-2):224-238.e10. PMID:28017329 doi:10.1016/j.cell.2016.11.042
7. ↑ Yoshinaka T, Kosako H, Yoshizumi T, Furukawa R, Hirano Y, Kuge O, Tamada T, Koshiba T. Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region. iScience. 2019 Sep 27;19:1065-1078. doi: 10.1016/j.isci.2019.08.056. Epub 2019, Sep 3. PMID:31522117 doi:http://dx.doi.org/10.1016/j.isci.2019.08.056
8. ↑ Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S. Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling. J Biol Chem. 2003 Nov 28;278(48):47853-61. PMID:14500729 doi:10.1074/jbc.M305171200
9. ↑ Zhang J, Sun Z, Wu Q, Shen J. Prohibitin 1 interacts with signal transducer and activator of transcription 3 in T-helper 17 cells. Immunol Lett. 2020 Mar;219:8-14. PMID:31899195 doi:10.1016/j.imlet.2019.12.008