ABSTRACT
Fork head box O (FOXO) transcription factor is a key player in an evolutionarily conserved pathway. The mammalian FOXO family consists of FOXO1, 3, 4 and 6, are highly similar in their structure, function and regulation. To maintain optimum body function, the organisms have developed complex mechanisms for homeostasis. Importantly, it is well known that when these mechanisms dysregulate it results in the development of age-related disease. FOXO proteins are involved in a diverse cellular function and also have clinical significance including cell cycle arrest, cell differentiation, tumour suppression, DNA repair, longevity, diabetic complications, immunity, wound healing, regulation of metabolism and thus treatment of several types of diseases. By the combinations of post-translational modifications FOXO's serve as a 'molecular code' to sense external stimuli and recruit it as to specific regions of the genome and provide an integrated cellular response to changing physiological conditions. Akt/Protein kinase B a signaling pathway as a main regulator of FOXO to perform a diverse function in organisms. The present review summarizes the molecular and clinical aspects of FOXO transcription factor. And also elaborate the interaction of FOXO with the nucleosome remodelling complex to target genes, which is essential to cellular homeostasis.
Subject(s)
Aging/genetics , Disease/genetics , Forkhead Transcription Factors/genetics , Gene Expression Regulation , Aging/metabolism , Animals , Cell Physiological Phenomena/genetics , Forkhead Transcription Factors/metabolism , Humans , Longevity/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , Signal Transduction/geneticsABSTRACT
Keap1-Nrf2 pathway is continuously involved in the cytoprotection from oxidative stress generated due to various factors either extrinsic or intrinsic in origin. This role of Nrf2 in the response to oxidative stress is well established. Following oxidative insult, Nrf2 mediates the regulation of the inducible expression of cytoprotective genes. The level and functional capacity of Nrf2 is regulated at the post-transcriptional level, mainly through its association with an actin-associated protein, Keap1. Various studies reported that any discrepancy from their routine may lead to promotion of tumor as well. So there is need to explore their role in cytoprotection and tumor promotion if any. This review is an attempt to critically analyze the available data that may lighten up the present knowledge and unveil the new regime for cancer prevention and treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm , NF-E2-Related Factor 2/metabolism , Neoplasms/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effects , Animals , Cytoprotection , Humans , Neoplasms/pathology , Neoplasms/prevention & controlABSTRACT
Mitochondria perform significant roles in cellular energy metabolism. Among others, these functions include free radicals generation, control of cell death, growth, development, integration of signals from mitochondria to nucleus and nucleus to mitochondria, and various metabolic pathways. The biological impact of a given mutation may vary, depending on the nature of the mutation and the proportion of mutant mtDNAs carried by the cell. Identification of mtDNA mutations in precancerous lesions supports their early contribution to cell transformation and cancer progression. Introduction of mtDNA mutations in transformed cells has been associated with increased ROS production and tumor growth. Studies reveal that increased and altered mtDNA plays a role in the development of cancer but further work is required to establish the functional significance of specific mitochondrial mutations in cancer and disease progression. This review briefly summarizes the recent progress in this field.