PHB: a pleiotropic membrane protein that suppresses cell proliferation, apoptosis and senescence. It plays a role both in maintaining mitochondrial integrity and in cell cycle regulation. Expression increases approximately 3-fold upon entry into G1 phase compared with other phases of the cell cycle. It helps prevent ROS-induced senescence and its expression decreases heterogeneously during cellular aging. Helps maintain the angiogenic capacity of endothelial cells. Up-regulated during activation of primary human T cells via CD3/CD28 pathways. Present in multiple cellular compartments. Large assemblies of PHB and PHB2 localize in the inner membrane of mitochondria. Acts as a mitochondrial chaperone protein, regulates mitochondrial morphogenesis, and helps regulate the organization of mitochondrial DNA. Reported to target lipid rafts. In the nucleus, it has been reported to interact with various transcription factors, modulating their activity. A potential tumor suppressor that functions as a potent transcriptional corepressor for estrogen receptor alpha. It is downregulated by androgens, and represses androgen receptor activity. Co-localizes with Rb in the nucleus and recruits N-CoR and HDAC1 for transcriptional repression. In vivo promoter occupancy studies have suggested that the PHB gene is a direct target of c-Myc. May bind to and enhance the transcriptional activity of p53. Both Phb and Phb2 are present in the circulation and can be internalized by cultured cells. Overexpressed in endometrioid ovarian adenocarcinoma and papillary serous ovarian carcinoma. Mutated in sporadic breast cancer.
Protein type: Mitochondrial; Motility/polarity/chemotaxis; Nuclear receptor co-regulator; Chaperone; Transcription, coactivator/corepressor; Apoptosis; Oncoprotein; Cell cycle regulation
Cellular Component: nucleoplasm; mitochondrial crista; mitochondrion; membrane; integral to plasma membrane; cytoplasm; mitochondrial inner membrane; extrinsic to mitochondrial outer membrane; nucleus; myelin sheath
Molecular Function: enzyme binding; histone deacetylase binding
Biological Process: osteoblast differentiation; transcription from RNA polymerase II promoter; negative regulation of cell proliferation; progesterone receptor signaling pathway; regulation of transcription, DNA-dependent; positive regulation of transcription, DNA-dependent; histone deacetylation; negative regulation of transcription from RNA polymerase II promoter; negative regulation of cell growth; negative regulation of transcription, DNA-dependent; negative regulation of apoptosis
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