The emerging roles of prohibitins in folliculogenesis

Abstract

Prohibitins are members of a highly conserved eukaryotic protein family containing the stomatin/ prohibitin/flotillin/HflK/C (SPFH) domain [also known as the prohibitin (PHB) domain] found in divergent species from prokaryotes to eukaryotes. Prohibitins are found in unicellular eukaryotes, fungi, plants, animals and humans. Prohibitins are ubiquitously expressed and present in multiple cellular compartments including the mitochondria, nucleus, and the plasma membrane, and shuttles between the mitochondria, cytosol and nucleus. Multiple functions have been attributed to the mitochondrial and nuclear prohibitins, including cellular differentiation, anti-proliferation, and morphogenesis. In the present review, we focus on the recent developments in prohibitins research related to folliculogenesis. Based on current research findings, the data suggest that these molecules play important roles in modulating specific responses of granulose cells to follicle stimulating hormone (FSH) by acting at multiple levels of the FSH signal transduction pathway. Understanding the molecular mechanisms by which the intracellular signaling pathways utilize prohibitins in governing folliculogenesis is likely to result in development of strategies to overcome fertility disorders and suppress ovarian cancer growth. KeywordsProhibitins; PHB; PHB2; Repressor Of Estrogen Receptor Action; REA; mitochondria; nucleus; Review INTRODUCTIONUnderstanding the mechanisms underlying the growth and development of a competent follicle with the capacity to release a fertilizable oocyte is a major goal of reproductive biology, particularly, since female infertility is clearly a major public health issue. Ovarian granulosa cells (GCs) play an important physiological role in supporting the development and selection of the dominant follicle by controlling oocyte maturation and by producing the steroid hormones, estrogen (E 2 ) and progesterone (P 4 ) that are critical for maintenance of the ovarian cycle. Mammalian ovarian follicular development is tightly regulated by (1-6). Based on current research findings, the data suggest that these molecules play important roles in modulating specific responses of GCs to follicle stimulating hormone (FSH) by acting at multiple levels of the FSH signal transduction pathway. Understanding the molecular mechanisms by which the intracellular signaling pathways utilize prohibitins in governing folliculogenesis is likely to result in development of strategies to overcome fertility disorders and suppress ovarian cancer growth. In the last decade, significant progress has been made in analyzing the expression, distribution and in determining the specific roles that the PHB and REA play in mammalian reproductive physiology. In the present review, we summarize some of the recent developments in PHB and REA research related to folliculogenesis. PROHIBITINSProhibitins are members of an extensive evolutionarily conserved family of proteins which includes stomatins, plasma membrane proteins of Escherichia coli (HflKC), f...

A novel prognostic marker and immunogenic membrane antigen: prohibitin (PHB) in pancreatic cancer

“…Prohibitin (PHB), including PHB1 (BAP32), PHB2 (BAP37, REA), PHB3 and PHB4, is ubiquitously expressed in multiple cellular compartments, including the mitochondria, the nucleus and the plasma membrane, and PHB is shuttled between the mitochondria, the cytosol and the nucleus 10–12 . PHB contains an N-terminal transmembrane domain that is an evolutionarily conserved PHB domain similar to that in lipid raft-associated proteins and a C-terminal coiled-coil domain that is involved in the regulation of protein-protein interactions 13–15 .…”