Multifaceted role of prohibitin in cell survival and apoptosis

Abstract

Human eukaryotic prohibitin (prohibitin-1 and prohibitin-2) is a membrane protein with different cellular localizations. It is involved in multiple cellular functions, including energy metabolism, proliferation, apoptosis, and senescence. The subcellular localization of prohibitin may determine its functions. Membrane prohibitin regulate the cellular signaling of membrane transport, nuclear prohibitin control transcription activation and the cell cycle, and mitochondrial prohibitin complex stabilize the mitochondrial genome and modulate mitochondrial dynamics, mitochondrial morphology, mitochondrial biogenesis, and the mitochondrial intrinsic apoptotic pathway. Moreover, prohibitin can translocates into the nucleus or the mitochondria under apoptotic signals and the subcellular shuttling of prohibitin is necessary for apoptosis process. Apoptosis is the process of programmed cell death that is important for the maintenance of normal physiological functions. Consequently, any alteration in the content, post-transcriptional modification (i.e. phosphorylation) or the nuclear or mitochondrial translocation of prohibitin may influence cell fate. Understanding the mechanisms of the expression and regulation of prohibitin may be useful for future research. This review provides an overview of the multifaceted and essential roles played by prohibitin in the regulation of cell survival and apoptosis.

Prohibitin 1 Regulates the H19-Igf2 Axis and Proliferation in Hepatocytes

“…Membranebound PHB1 regulates downstream signaling pathways, whereas mitochondrial and nuclear PHB1 regulates apoptosis, transcriptional activation, and cell cycle, indicating the important link between its cellular localization and function (2,3) Studies have demonstrated that PHB1 protects cells from oxidative stress and maintains the functional integrity of the mitochondria (2,4,5). Nuclear PHB1 co-localizes with p53, E2F1, and retinoblastoma protein (6 -8).…”

“…Nuclear PHB1 co-localizes with p53, E2F1, and retinoblastoma protein (6 -8). In breast cancer and B-cell lymphoma cell lines, Phb1 overexpression induces p53 transcriptional activity, whereas it represses E2F1-mediated transcription via its interaction with the retinoblastoma protein (3,9). Despite this strong evidence of anti-tumorigenic properties of PHB1, a number of studies have indicated the pro-tumorigenic effects of PHB1.…”

“…These genes are part of a well characterized cluster that contains the paternally expressed Igf2 and maternally expressed H19. Both genes share enhancers and are asynchronously regulated at a site called the imprinting control region (ICR) 3 (13). Loss of imprinting of both Igf2 and H19 has been observed in hepatocellular carcinoma (HCC) tissues and cell lines (14,15).…”

Investigação de parceiros moleculares de Cdc42 em linhagens de células humanas submetidas a estresse genotóxico

“…A mutação V12 é equivalente a encontrada naturalmente na proteína oncogênica de Ras, onde Ras V12 apresenta ganho de função (Val→Gly na posição 12), esse mutação causa uma perda da capacidade intrínseca e mediada por GAPs de hidrólise de GTP, tornandose constitutivamente ativo (Qiu et al, 1995 Esse complexo proteico está envolvido em diversas funções celulares, tais como proliferação, apoptose e senescência (Peng et al 2015). A Proibitina de membrana regula o transporte celular e pode causar a parada do ciclo celular entre as fases G0…”

Efeito da lectina ArtinM na hepatocarcinogênese induzida por Aflatoxina B1

“…A PBT é uma proteína que atua como supressora tumoral por meio da inibição da atividade do fator de transcrição E2F ou do estímulo à atividade de p53, resultando na redução da proliferação celular e na indução de apoptose (WANG et al, 2002;FUSARO et al, 2003;SÁNCHEZ-QUILES et al, 2010;PENG et al, 2015;RAMANI et al, 2016). Neste estudo, verificou-se que as expressões gênica e proteica de PBT no fígado dos animais intoxicados por AFB1 e tratados com ArtinM foram significativamente maiores em comparação aos animais apenas intoxicados por AFB1.…”