The role of the forkhead transcription factor, Foxc1, in the development of the mouse lacrimal gland

Hcm1 is a member of the forkhead transcription factor family involved in segregation, spindle pole dynamics, and budding in Saccharomyces cerevisiae. Our group described the role of Hcm1 in mitochondrial biogenesis and stress resistance, and in the cellular adaptation to mitochondrial respiratory metabolism when nutrients decrease. Regulation of Hcm1 activity occurs at the protein level, subcellular localization, and transcriptional activity. Here we report that the amount of protein increased in the G1/S transition phase when the factor accumulated in the nucleus. In the G2/M phases, the Hcm1 amount decreased, and it was translocated outside the nucleus with a network-like localization. Preparation of highly purified mitochondria by a sucrose gradient density demonstrated that Hcm1 colocalized with mitochondrial markers, inducing expression of COX1, a mitochondrial encoded subunit of cytochrome oxidase, in the G2/M phases. Taken together, these results show a new localization of Hcm1 and suggest that it acts as a mitochondrial transcription factor regulating the metabolism of this organelle.

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The Role of the Forkhead Transcription Factor, FOXM1, in Pituitary Gland Development

10.1210/endo-meetings.2011.part2.p2.p1-384 ◽

2011 ◽

pp. P1-384-P1-384

Author(s):

Adam Gerrit Ploegman ◽

Buffy S Ellsworth

Keyword(s):

Transcription Factor ◽

Pituitary Gland ◽

Forkhead Transcription Factor ◽

Gland Development

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Hypertrophic cardiomyopathy in high-fat diet-induced obesity: role of suppression of forkhead transcription factor and atrophy gene transcription

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00319.2008 ◽

2008 ◽

Vol 295 (3) ◽

pp. H1206-H1215 ◽

Cited By ~ 72

Author(s):

Cindy X. Fang ◽

Feng Dong ◽

D. Paul Thomas ◽

Heng Ma ◽

Leilei He ◽

...

Keyword(s):

Transcription Factor ◽

Palmitic Acid ◽

High Fat Diet ◽

Weight Control ◽

Dominant Negative ◽

High Fat ◽

Forkhead Transcription Factor ◽

Diet Induced Obesity ◽

Intracellular Ca

Cellular hypertrophy is regulated by coordinated pro- and antigrowth machineries. Foxo transcription factors initiate an atrophy-related gene program to counter hypertrophic growth. This study was designed to evaluate the role of Akt, the forkhead transcription factor Foxo3a, and atrophy genes muscle-specific RING finger (MuRF)-1 and atrogin-1 in cardiac hypertrophy and contractile dysfunction associated with high-fat diet-induced obesity. Mice were fed a low- or high-fat diet for 6 mo along with a food-restricted high-fat weight control group. Echocardiography revealed decreased fractional shortening and increased end-systolic diameter and cardiac hypertrophy in high-fat obese but not in weight control mice. Cardiomyocytes from high-fat obese but not from weight control mice displayed contractile and intracellular Ca2+ defects including depressed maximal velocity of shortening/relengthening, prolonged duration of shortening/relengthening, and reduced intracellular Ca2+ rise and clearance. Caspase activities were greater in high-fat obese but not in weight control mouse hearts. Western blot analysis revealed enhanced basal Akt and Foxo3a phosphorylation and reduced insulin-stimulated phosphorylation of Akt and Foxo3a without changes in total protein expression of Akt and Foxo3a in high-fat obese hearts. RT-PCR and immunoblotting results displayed reduced levels of the atrogens atrogin-1 and MuRF-1, the upregulated hypertrophic markers GATA4 and ciliary neurotrophic factor receptor-α, as well as the unchanged calcineurin and proteasome ubiquitin in high-fat obese mouse hearts. Transfection of H9C2 myoblast cells with dominant-negative Foxo3a adenovirus mimicked palmitic acid (0.8 mM for 24 h)-induced GATA4 upregulation without an additive effect. Dominant-negative Foxo3a-induced upregulation of pAkt and repression of phosphatase and tensin homologue were abrogated by palmitic acid. These results suggest a cardiac hypertrophic response in high-fat diet-associated obesity at least in part through inactivation of Foxo3a by the Akt pathway.

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FOXL2: a central transcription factor of the ovary

Journal of Molecular Endocrinology ◽

10.1530/jme-13-0159 ◽

2013 ◽

Vol 52 (1) ◽

pp. R17-R33 ◽

Cited By ~ 67

Author(s):

Adrien Georges ◽

Aurelie Auguste ◽

Laurianne Bessière ◽

Anne Vanet ◽

Anne-Laure Todeschini ◽

...

Keyword(s):

Transcription Factor ◽

Forkhead Transcription Factor ◽

Gene Encoding ◽

Post Translational Modifications ◽

Forkhead Box ◽

Molecular Aspects ◽

And Function ◽

Craniofacial Defects ◽

The Impact

Forkhead box L2 (FOXL2) is a gene encoding a forkhead transcription factor preferentially expressed in the ovary, the eyelids and the pituitary gland. Its germline mutations are responsible for the blepharophimosis ptosis epicanthus inversus syndrome, which includes eyelid and mild craniofacial defects associated with primary ovarian insufficiency. Recent studies have shown the involvement of FOXL2 in virtually all stages of ovarian development and function, as well as in granulosa cell (GC)-related pathologies. A central role of FOXL2 is the lifetime maintenance of GC identity through the repression of testis-specific genes. Recently, a highly recurrent somatic FOXL2 mutation leading to the p.C134W subtitution has been linked to the development of GC tumours in the adult, which account for up to 5% of ovarian malignancies. In this review, we summarise data on FOXL2 modulators, targets, partners and post-translational modifications. Despite the progresses made thus far, a better understanding of the impact of FOXL2 mutations and of the molecular aspects of its function is required to rationalise its implication in various pathophysiological processes.

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Involvement of Transcription Factor FoxO1 in the Pathogenesis of Polycystic Ovary Syndrome

Frontiers in Physiology ◽

10.3389/fphys.2021.649295 ◽

2021 ◽

Vol 12 ◽

Author(s):

Renfeng Xu ◽

Zhengchao Wang

Keyword(s):

Transcription Factor ◽

Polycystic Ovary Syndrome ◽

Inflammatory Response ◽

Polycystic Ovary ◽

Cell Types ◽

Low Grade ◽

Childbearing Age ◽

Forkhead Transcription Factor ◽

Ovary Syndrome

FoxO1 is a member of the forkhead transcription factor family subgroup O (FoxO), which is expressed in many cell types, and participates in various pathophysiological processes, including cell proliferation, apoptosis, autophagy, metabolism, inflammatory response, cytokine expression, immune differentiation, and oxidative stress resistance. Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in the women of childbearing age, which is regulated via a variety of signaling pathways. Currently, the specific mechanism underlying the pathogenesis of PCOS is still unclear. As an important transcription factor, FoxO1 activity might be involved in the pathophysiology of PCOS. PCOS has been associated with insulin resistance and low-grade inflammatory response. Therefore, the studies regarding the role of FoxO1 in the incidence and associated complications of PCOS will help provide novel ideas for establishing the treatment strategy of PCOS.

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