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PMID:26475860

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Citation

'Cardozo Gizzi, AM, Prucca, CG, Gaveglio, VL, Renner, ML, Pasquare, SJ and Caputto, BL (2015) The catalytic efficiency of Lipin 1β increases by physically interacting with the protooncoprotein c-Fos. J. Biol. Chem. '

Abstract

Phosphatidic acid (PA) is a central precursor for membrane phospholipid biosynthesis. Lipin family is a Mg-dependent type I PA phosphatase, involved in de novo synthesis of neutral lipids and of phospholipids. The regulation of Lipin activity may govern the pathways by which these lipids are synthesized and control the cellular levels of important signaling lipids. On the other hand, the proto-oncoprotein c-Fos has an emerging role in glycerolipid synthesis regulation: by interacting with key synthetizing enzymes it is able to increase overall phopho- and glyco- lipid synthesis. We studied the Lipin 1β enzyme activity in a cell-free system using PA/Triton X-100 mixed micelles as substrate, analyzing it in the presence/absence of c-Fos. We found that Lipin 1β kcat increases around 40% in the presence of c-Fos, with no change in the Lipin 1β affinity for the PA/Triton X-100 mixed micelles. We also probed a physical interaction between both proteins. While the c-Fos domain involved in Lipin activation is its basic domain (BD), the interaction domain is mapped to the c-Fos N-terminal. In conclusion, we provide evidence for a novel positive regulator of Lipin 1β PA phosphatase activity that is not achieved via altering its subcellular localization or affinity for membranes but rather through directly increasing its catalytic efficiency.

Links

PubMed Online version:10.1074/jbc.M115.678821

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:LPIN1

GO:0005783: endoplasmic reticulum

ECO:0000314:

C

Figure 6b,e and f

complete
CACAO 11041

MOUSE:LPIN1

GO:0005634: nucleus

ECO:0000314:

C

Figure 5b

complete
CACAO 11042

MOUSE:LPIN1

GO:0005737: cytoplasm

ECO:0000314:

C

Figure 5b

complete
CACAO 11043

MOUSE:FOS

GO:0005783: endoplasmic reticulum

ECO:0000314:

C

Figure 6a, d and f

complete
CACAO 11044

MOUSE:FOS

GO:0005634: nucleus

ECO:0000314:

C

Figure 5a

complete
CACAO 11045

MOUSE:FOS

GO:0005737: cytoplasm

ECO:0000314:

C

Figure 5 a

complete
CACAO 11046

Notes

See also

References

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