REG1 Binds to Protein Phosphatase Type 1 and Regulates Glucose Repression in Saccharomyces Cerevisiae

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1995 Dec 1

PMID 8846786

Citations 113

Authors

J Tu

M Carlson

Affiliations

Soon will be listed here.

Abstract

Protein phosphatase type 1 (PP1) is encoded by GLC7, an essential gene in Saccharomyces cerevisiae. The GLC7 phosphatase is required for glucose repression and appears to function antagonistically to the SNF1 protein kinase. Previously, we characterized a mutation, glc7-T152K, that relieves glucose repression but does not interfere with the function of GLC7 in glycogen metabolism. We proposed that the mutant GLC7T152K phosphatase is defective in its interaction with a regulatory subunit that directs participation of PP1 in the glucose repression mechanism. Here, we present evidence that REG1, a protein required for glucose repression, is one such regulatory subunit. We show that REG1 is physically associated with GLC7. REG1 interacts with GLC7 strongly and specifically in the two-hybrid system, and REG1 and GLC7 fusion proteins co-immunoprecipitate from cell extracts. Moreover, overexpression of a REG1 fusion protein suppresses the glc7-T152K mutant defect in glucose repression. This and other genetic evidence indicate that the two proteins function together in regulating glucose repression. These results suggest that REG1 is a regulatory subunit of PP1 that targets its activity to proteins in the glucose repression regulatory pathway.

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References

Tu J, Vallier L, Carlson M . Molecular and genetic analysis of the SNF7 gene in Saccharomyces cerevisiae. Genetics. 1993; 135(1):17-23. PMC: 1205616. DOI: 10.1093/genetics/135.1.17. View

Fields S, Song O . A novel genetic system to detect protein-protein interactions. Nature. 1989; 340(6230):245-6. DOI: 10.1038/340245a0. View

Cohen P . The structure and regulation of protein phosphatases. Annu Rev Biochem. 1989; 58:453-508. DOI: 10.1146/annurev.bi.58.070189.002321. View

Durfee T, Becherer K, Chen P, Yeh S, Yang Y, Kilburn A . The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 1993; 7(4):555-69. DOI: 10.1101/gad.7.4.555. View

Breeden L, Nasmyth K . Regulation of the yeast HO gene. Cold Spring Harb Symp Quant Biol. 1985; 50:643-50. DOI: 10.1101/sqb.1985.050.01.078. View

Bischoff F, Krebber H, Kempf T, Hermes I, Ponstingl H . Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport. Proc Natl Acad Sci U S A. 1995; 92(5):1749-53. PMC: 42597. DOI: 10.1073/pnas.92.5.1749. View

Matsumoto K, Yoshimatsu T, Oshima Y . Recessive mutations conferring resistance to carbon catabolite repression of galactokinase synthesis in Saccharomyces cerevisiae. J Bacteriol. 1983; 153(3):1405-14. PMC: 221791. DOI: 10.1128/jb.153.3.1405-1414.1983. View

Kinoshita N, Ohkura H, Yanagida M . Distinct, essential roles of type 1 and 2A protein phosphatases in the control of the fission yeast cell division cycle. Cell. 1990; 63(2):405-15. DOI: 10.1016/0092-8674(90)90173-c. View

Niederacher D, Entian K . Characterization of Hex2 protein, a negative regulatory element necessary for glucose repression in yeast. Eur J Biochem. 1991; 200(2):311-9. DOI: 10.1111/j.1432-1033.1991.tb16187.x. View

10.

Francisco L, Wang W, Chan C . Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation. Mol Cell Biol. 1994; 14(7):4731-40. PMC: 358846. DOI: 10.1128/mcb.14.7.4731-4740.1994. View

11.

Stone E, Yamano H, Kinoshita N, Yanagida M . Mitotic regulation of protein phosphatases by the fission yeast sds22 protein. Curr Biol. 1993; 3(1):13-26. DOI: 10.1016/0960-9822(93)90140-j. View

12.

Treitel M, Carlson M . Repression by SSN6-TUP1 is directed by MIG1, a repressor/activator protein. Proc Natl Acad Sci U S A. 1995; 92(8):3132-6. PMC: 42119. DOI: 10.1073/pnas.92.8.3132. View

13.

Feng Z, Wilson S, Peng Z, Schlender K, Reimann E, Trumbly R . The yeast GLC7 gene required for glycogen accumulation encodes a type 1 protein phosphatase. J Biol Chem. 1991; 266(35):23796-801. View

14.

Chien C, Bartel P, Sternglanz R, Fields S . The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. Proc Natl Acad Sci U S A. 1991; 88(21):9578-82. PMC: 52761. DOI: 10.1073/pnas.88.21.9578. View

15.

Tung K, Norbeck L, Nolan S, Atkinson N, Hopper A . SRN1, a yeast gene involved in RNA processing, is identical to HEX2/REG1, a negative regulator in glucose repression. Mol Cell Biol. 1992; 12(6):2673-80. PMC: 364461. DOI: 10.1128/mcb.12.6.2673-2680.1992. View

16.

Axton J, Dombradi V, Cohen P, Glover D . One of the protein phosphatase 1 isoenzymes in Drosophila is essential for mitosis. Cell. 1990; 63(1):33-46. DOI: 10.1016/0092-8674(90)90286-n. View

17.

Wek R, CANNON J, Dever T, Hinnebusch A . Truncated protein phosphatase GLC7 restores translational activation of GCN4 expression in yeast mutants defective for the eIF-2 alpha kinase GCN2. Mol Cell Biol. 1992; 12(12):5700-10. PMC: 360510. DOI: 10.1128/mcb.12.12.5700-5710.1992. View

18.

Sikorski R, Hieter P . A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989; 122(1):19-27. PMC: 1203683. DOI: 10.1093/genetics/122.1.19. View

19.

Ohkura H, Kinoshita N, Miyatani S, Toda T, Yanagida M . The fission yeast dis2+ gene required for chromosome disjoining encodes one of two putative type 1 protein phosphatases. Cell. 1989; 57(6):997-1007. DOI: 10.1016/0092-8674(89)90338-3. View

20.

Ohkura H, Yanagida M . S. pombe gene sds22+ essential for a midmitotic transition encodes a leucine-rich repeat protein that positively modulates protein phosphatase-1. Cell. 1991; 64(1):149-57. DOI: 10.1016/0092-8674(91)90216-l. View