Smurf1 directly targets hPEM-2, a GEF for Cdc42, via a novel combination of protein interaction modules in the ubiquitin-proteasome pathway
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Kei Yamaguchi
Abstract
Smurf1, a member of HECT-type E3 ubiquitin ligases, regulates cell polarity and protrusive activity by inducing ubiquitination and subsequent proteasomal degradation of the small GTPase RhoA. We report here that hPEM-2, a guanine nucleotide exchange factor for the small GTPase Cdc42, is a novel target of Smurf1. Pulse-chase labeling and a ubiquitination experiment using MG132, a proteasomal inhibitor, indicate that Smurf1 induces proteasomal degradation of hPEM-2 in cells. GST pull-down assays with heterologously expressed firefly luciferase-fusion proteins that include partial sequences of hPEM-2 reveal that part of the PH domain (residues 318–343) of hPEM-2 is sufficient for binding to Smurf1. In contrast, the hPEM-2 binding domain in Smurf1 was mapped to the C2 domain. Although it has been reported that the binding activities of some C2 domains to target proteins are regulated by Ca2+, Smurf1 interacts with hPEM-2 in a Ca2+-independent manner. Our discovery that hPEM-2 is, in addition to RhoA, a target protein of Smurf1 suggests that Smurf1 plays a crucial role in the spatio-temporal regulation of Rho GTPase family members.
©2008 by Walter de Gruyter Berlin New York
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- The histone H1 family: specific members, specific functions?
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- Role of histone modifications in defining chromatin structure and function
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- Smurf1 directly targets hPEM-2, a GEF for Cdc42, via a novel combination of protein interaction modules in the ubiquitin-proteasome pathway
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- Ribosome display and selection of human anti-CD22 scFvs derived from an acute lymphocytic leukemia patient
- Sub-chronic administration of the 11β-HSD1 inhibitor, carbenoxolone, improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity
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Artikel in diesem Heft
- Highlight: 59th Mosbach Kolloquium
- The role of long non-coding RNAs in chromatin structure and gene regulation: variations on a theme
- The histone H1 family: specific members, specific functions?
- ATP-dependent chromatosome remodeling
- Role of histone modifications in defining chromatin structure and function
- Differential loss of histone H3 isoforms mono-, di- and tri-methylated at lysine 4 during X-inactivation in female embryonic stem cells
- Disentanglement of protease substrate repertoires
- p53-dependent repression of the human MCL-1 gene encoding an anti-apoptotic member of the BCL-2 family: the role of Sp1 and of basic transcription factor binding sites in the MCL-1 promoter
- 5′-End maturation of tRNA in Aquifex aeolicus
- Smurf1 directly targets hPEM-2, a GEF for Cdc42, via a novel combination of protein interaction modules in the ubiquitin-proteasome pathway
- Purification and characterization of natural Ara h 8, the Bet v 1 homologous allergen from peanut, provides a novel isoform
- Human butyrylcholinesterase components differ in aryl acylamidase activity
- Ribosome display and selection of human anti-CD22 scFvs derived from an acute lymphocytic leukemia patient
- Sub-chronic administration of the 11β-HSD1 inhibitor, carbenoxolone, improves glucose tolerance and insulin sensitivity in mice with diet-induced obesity
- Inhibitory effect of the sugarcane cystatin CaneCPI-4 on cathepsins B and L and human breast cancer cell invasion
