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Physiological functions of FBW7 in cancer and metabolism.

ABSTRACT: FBW7 is one of the most well characterized F-box proteins that serve as substrate recognition subunits of SCF (Skp1-Cullin 1-F-box proteins) E3 ubiquitin ligase complexes. SCFFBW7 plays key roles in regulating cell cycle progression, differentiation, and stem cell maintenance largely through targeting a broad range of oncogenic substrates for proteasome-dependent degradation. The identification of an increasing number of FBW7 substrates for ubiquitination, and intensive in vitro and in vivo studies have revealed a network of signaling components controlled by FBW7 that contributes to metabolic regulation as well as its tumor suppressor role. Here we mainly focus on recent findings that highlight a critical role for FBW7 in cancer and metabolism.

SUBMITTER: Shimizu K

PROVIDER: S-EPMC5882551 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Physiological functions of FBW7 in cancer and metabolism.

Shimizu Kouhei K Nihira Naoe Taira NT Inuzuka Hiroyuki H Wei Wenyi W

Cellular signalling 20180221

FBW7 is one of the most well characterized F-box proteins that serve as substrate recognition subunits of SCF (Skp1-Cullin 1-F-box proteins) E3 ubiquitin ligase complexes. SCF<sup>FBW7</sup> plays key roles in regulating cell cycle progression, differentiation, and stem cell maintenance largely through targeting a broad range of oncogenic substrates for proteasome-dependent degradation. The identification of an increasing number of FBW7 substrates for ubiquitination, and intensive in vitro and i ...[more]

PMID: 29474981

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Project description:Background:Fat storage is required for the life cycle of many organisms. The primary fat depot for most vertebrates is white adipose tissue. However, in primitive vertebrates (e.g., agnathan group and elasmobranchs), the liver is usually responsible for fat storage. Among the vertebrates, amphibians have a unique status, as their larvae live in the water and exhibit some primitive traits that are similar to fish. Although it has been recognized that adult frogs use their abdominal white adipose tissue as a primary fat depot, how tadpoles store their fat is still inconclusive. The metabolic traits and physiological functions of primitive fat depots may have wide-ranging implications on the pathology of abnormal lipid deposition in mammals and the evolution of fat storage. Results:Rana omeimontis tadpoles used their liver as the primary fat depot. In sufficiently fed tadpoles at stage 30-31, the hepatosomatic index (HSI) reached up to 7%, and triglycerides (TG) accounted for 15% of liver weight. Their liver resembled white adipose tissue in histological morphology, characterized by polygonal hepatocytes filled with fat. Their liver metabolic composition was unique, characterized by the dominance of maltotriose, arachidonic acid and dipeptides in soluble carbohydrates, free fatty acids and amino acids. Hepatic fat was the major metabolic fuel of fasted R. omeimontis tadpoles, which had similar reserve mobilization and allocation patterns as mammals. From a developmental perspective, hepatic fat was important to fuel late metamorphic climax. Interestingly, starvation induced accelerated metamorphosis in tadpoles with high HSI (4.96?±?0.21%). However, this phenomenon was not observed in tadpoles with low HSI (2.71?±?0.16%), even though they had similar initial body weight and developmental stage. Hepatic fat abundance was the most prominent difference between the two groups. Conclusion:To the best of our knowledge, this is the first report that liver can be the primary fat depot in vertebrates with higher evolutionary status than bony fish. The unique hepatic histological and metabolic traits likely either guard their liver against lipotoxicity or make their hepatocytes adapt to fat accumulation. This fatty liver could be a primitive counterpart of mammalian white adipose tissue (WAT). In addition, our study showed that the hepatic reserves of tadpoles, especially TG content, may provide body condition signals to modulate metamorphosis.

Dataset Information

Physiological functions of FBW7 in cancer and metabolism.

Publications

Physiological functions of FBW7 in cancer and metabolism.

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