SREBP in signal transduction: cholesterol metabolism and beyond

Current Opinion in Cell Biology

Volumn 19, Issue 2, 2007, Pages 215-222

  Bengoechea Alonso, Maria T ^a   Ericsson, Johan ^a  

^a UPPSALA UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; LIPID; PROTEASOME; STEROL REGULATORY ELEMENT BINDING PROTEIN; TRANSCRIPTION FACTOR; UBIQUITIN PROTEIN LIGASE;

BACTERIAL INFECTION; CELL CYCLE PROGRESSION; CELL SURVIVAL; CHOLESTEROL METABOLISM; ENDOPLASMIC RETICULUM; FEEDBACK SYSTEM; GOLGI COMPLEX; HUMAN; INTRACELLULAR TRANSPORT; METABOLIC REGULATION; NONHUMAN; OXYGEN SENSING; PHAGOCYTOSIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN DNA BINDING; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; PROTEIN TRANSPORT; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TRANSCRIPTOMICS;

AMINO ACID SEQUENCE; ANIMALS; CELL NUCLEUS; CHOLESTEROL; HUMANS; HYDROXYMETHYLGLUTARYL COA REDUCTASES; LIPIDS; MODELS, BIOLOGICAL; MODELS, GENETIC; MOLECULAR SEQUENCE DATA; PROTEIN PROCESSING, POST-TRANSLATIONAL; SIGNAL TRANSDUCTION; STEROL REGULATORY ELEMENT BINDING PROTEINS;

BACTERIA (MICROORGANISMS);

EID: 33847709027     PISSN: 09550674     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ceb.2007.02.004     Document Type: Review

References (40)

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23. •].
24. •] demonstrate that two different transcription factors, SREBP and NHR-49, regulate lipid metabolism in C. elegans through interactions with the same Mediator subunit, MDT-15.
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36. Hughes A.L., Todd B.L., and Espenshade P.J. SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast. Cell 120 (2005) 831-842. By sequence searches, the authors identify homologs of SREBP, Insig-1 and Scap in fission yeast. One of the two SREBP homologs is cleaved and activated in response to sterol-depletion in a Scap-dependent manner. However, Insig fails to regulate the activation of SREBP. Importantly, the authors show that SREBP in fission yeast is activated in response to hypoxia and that SREBP is required by fission yeast during anaerobic growth. Their results suggest that yeast may use oxygen-dependent sterol synthesis to monitor oxygen supply. The possibility that a similar system could exist in mammalian cells is exciting, especially considering the link between hypoxia and cancer.
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38. Gurcel L., Abrami L., Girardin S., Tschopp J., and van der Goot F.G. Caspase-1 activation of lipid metabolic pathways in response to bacterial pore-forming toxins promotes cell survival. Cell 126 (2006) 1135-1145. This paper reports the unexpected observation that SREBP1 and SREBP2 are cleaved and activated by bacterial pore-forming toxins. The activation of the SREBPs requires Scap, S1P and S2P. Surprisingly, the activation also requires the activation of caspase-1, and it is demonstrated that caspase-1 is activated by the inflammasome in response to potassium efflux through the pores. The results indicate that the SREBP-dependent increase in lipid synthesis supports the survival of infected cells. This study is an example of the broad role of lipid metabolism in cell biology.
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