title: An N-end rule pathway that recognizes proline and destroys gluconeogenic enzymes.
abstract: Cells synthesize glucose if deprived of it, and destroy gluconeogenic enzymes upon return to glucose-replete conditions. We found that the Gid4 subunit of the ubiquitin ligase GID in the yeast Saccharomyces cerevisiae targeted the gluconeogenic enzymes Fbp1, Icl1, and Mdh2 for degradation. Gid4 recognized the N-terminal proline (Pro) residue and the ~5-residue-long adjacent sequence motifs. Pck1, the fourth gluconeogenic enzyme, contains Pro at position 2; Gid4 directly or indirectly recognized Pro at position 2 of Pck1, contributing to its targeting. These and related results identified Gid4 as the recognition component of the GID-based proteolytic system termed the Pro/N-end rule pathway. Substrates of this pathway include gluconeogenic enzymes that bear either the N-terminal Pro residue or a Pro at position 2, together with adjacent sequence motifs.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Shun-Jia
authors.initials: SJ
authors.lastname: Chen
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Wadas
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Jang-Hyun
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. avarsh@caltech.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Varshavsky
mesh_terms: D006597:Fructose-Bisphosphatase / Q000737:chemistry / Q000378:metabolism; D005943:Gluconeogenesis; D005947:Glucose / Q000172:deficiency; D007522:Isocitrate Lyase / Q000737:chemistry / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000737:chemistry / Q000378:metabolism*; D011493:Protein Kinase C / Q000737:chemistry / Q000378:metabolism; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C111452:VID24 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D011392:Proline; C000614940:MDH2 protein, S cerevisiae; D008291:Malate Dehydrogenase; D011493:Protein Kinase C; C111172:FBP1 protein, S cerevisiae; D006597:Fructose-Bisphosphatase; C542285:ICL1 protein, S cerevisiae; D007522:Isocitrate Lyase; D005947:Glucose