CAC3 (MSI1) suppression of RAS2G19V is independent of chromatin assembly factor I and mediated by NPR1

S. D. Johnston, S. Enomoto, Lisa Schneper, M. C. McClellan, F. Twu, N. D. Montgomery, S. A. Haney, James Broach, J. Berman

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Cac3p/Msi1p, the Saccharomyces cerevisiae homolog of retinoblastoma-associated protein 48 (RbAp48), is a component of chromatin assembly factor I (CAF, a complex that assembles histories H3 and H4 onto replicated DNA. CAC3 overexpression also suppresses the RAS/cyclic AMP (cAMP) signal transduction pathway by an unknown mechanism. We investigated this mechanism and found that CAC3 suppression of RAS/cAMP signal transduction was independent of either CAC1 or CAC2, subunits required for CAF-I function. CAC3 suppression was also independent of other chromatin-modifying activities, indicating that Cac3p has at least two distinct, separable functions, one in chromatin assembly and one in regulating RAS function. Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm. In addition, Cac3p associates with Npr1p, a cytoplasmic kinase that stablizes several nutrient transporters by antagonizing a ubiquitin-mediated protein degradation pathway. Deletion of NPR1, like overexpression of Cac3p, suppressed the RAS/cAMP pathway. Furthermore, NPR1 overexpression interfered with the ability of CAC3 to suppress the RAS/cAMP pathway, indicating that extra Cac3p suppresses the RAS/cAMP pathway by sequestering Npr1p. Deletion of NPR1 did not affect the quantity, phosphorylation state, or localization of Ras2p. Consistent with the idea that Npr1p exerts its effect on the RAS/cAMP pathway by antagonizing a ubiquitin-mediated process, excess ubiquitin suppressed both the heat shock sensitivity and the sporulation defects caused by constitutive activation of the RAS/cAMP pathway. Thus, CAC3/MSI1 regulates the RAS/cAMP pathway via a chromatin-independent mechanism that involves the sequestration of Npr1p and may be due to the increased ubiquitination of an Npr1p substrate.

Original languageEnglish (US)
Pages (from-to)1784-1794
Number of pages11
JournalMolecular and cellular biology
Volume21
Issue number5
DOIs
StatePublished - Feb 26 2001

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Chromatin Assembly and Disassembly
Cyclic AMP
Ubiquitin
Chromatin
Signal Transduction
Retinoblastoma Protein
Ubiquitination
Proteolysis
Saccharomyces cerevisiae
Shock
Cytoplasm
Phosphotransferases
Hot Temperature
Phosphorylation
Food
DNA

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Johnston, S. D., Enomoto, S., Schneper, L., McClellan, M. C., Twu, F., Montgomery, N. D., ... Berman, J. (2001). CAC3 (MSI1) suppression of RAS2G19V is independent of chromatin assembly factor I and mediated by NPR1. Molecular and cellular biology, 21(5), 1784-1794. https://doi.org/10.1128/MCB.21.5.1784-1794.2001
Johnston, S. D. ; Enomoto, S. ; Schneper, Lisa ; McClellan, M. C. ; Twu, F. ; Montgomery, N. D. ; Haney, S. A. ; Broach, James ; Berman, J. / CAC3 (MSI1) suppression of RAS2G19V is independent of chromatin assembly factor I and mediated by NPR1. In: Molecular and cellular biology. 2001 ; Vol. 21, No. 5. pp. 1784-1794.
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Johnston, SD, Enomoto, S, Schneper, L, McClellan, MC, Twu, F, Montgomery, ND, Haney, SA, Broach, J & Berman, J 2001, 'CAC3 (MSI1) suppression of RAS2G19V is independent of chromatin assembly factor I and mediated by NPR1', Molecular and cellular biology, vol. 21, no. 5, pp. 1784-1794. https://doi.org/10.1128/MCB.21.5.1784-1794.2001

CAC3 (MSI1) suppression of RAS2G19V is independent of chromatin assembly factor I and mediated by NPR1. / Johnston, S. D.; Enomoto, S.; Schneper, Lisa; McClellan, M. C.; Twu, F.; Montgomery, N. D.; Haney, S. A.; Broach, James; Berman, J.

In: Molecular and cellular biology, Vol. 21, No. 5, 26.02.2001, p. 1784-1794.

Research output: Contribution to journalArticle

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T1 - CAC3 (MSI1) suppression of RAS2G19V is independent of chromatin assembly factor I and mediated by NPR1

AU - Johnston, S. D.

AU - Enomoto, S.

AU - Schneper, Lisa

AU - McClellan, M. C.

AU - Twu, F.

AU - Montgomery, N. D.

AU - Haney, S. A.

AU - Broach, James

AU - Berman, J.

PY - 2001/2/26

Y1 - 2001/2/26

N2 - Cac3p/Msi1p, the Saccharomyces cerevisiae homolog of retinoblastoma-associated protein 48 (RbAp48), is a component of chromatin assembly factor I (CAF, a complex that assembles histories H3 and H4 onto replicated DNA. CAC3 overexpression also suppresses the RAS/cyclic AMP (cAMP) signal transduction pathway by an unknown mechanism. We investigated this mechanism and found that CAC3 suppression of RAS/cAMP signal transduction was independent of either CAC1 or CAC2, subunits required for CAF-I function. CAC3 suppression was also independent of other chromatin-modifying activities, indicating that Cac3p has at least two distinct, separable functions, one in chromatin assembly and one in regulating RAS function. Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm. In addition, Cac3p associates with Npr1p, a cytoplasmic kinase that stablizes several nutrient transporters by antagonizing a ubiquitin-mediated protein degradation pathway. Deletion of NPR1, like overexpression of Cac3p, suppressed the RAS/cAMP pathway. Furthermore, NPR1 overexpression interfered with the ability of CAC3 to suppress the RAS/cAMP pathway, indicating that extra Cac3p suppresses the RAS/cAMP pathway by sequestering Npr1p. Deletion of NPR1 did not affect the quantity, phosphorylation state, or localization of Ras2p. Consistent with the idea that Npr1p exerts its effect on the RAS/cAMP pathway by antagonizing a ubiquitin-mediated process, excess ubiquitin suppressed both the heat shock sensitivity and the sporulation defects caused by constitutive activation of the RAS/cAMP pathway. Thus, CAC3/MSI1 regulates the RAS/cAMP pathway via a chromatin-independent mechanism that involves the sequestration of Npr1p and may be due to the increased ubiquitination of an Npr1p substrate.

AB - Cac3p/Msi1p, the Saccharomyces cerevisiae homolog of retinoblastoma-associated protein 48 (RbAp48), is a component of chromatin assembly factor I (CAF, a complex that assembles histories H3 and H4 onto replicated DNA. CAC3 overexpression also suppresses the RAS/cyclic AMP (cAMP) signal transduction pathway by an unknown mechanism. We investigated this mechanism and found that CAC3 suppression of RAS/cAMP signal transduction was independent of either CAC1 or CAC2, subunits required for CAF-I function. CAC3 suppression was also independent of other chromatin-modifying activities, indicating that Cac3p has at least two distinct, separable functions, one in chromatin assembly and one in regulating RAS function. Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm. In addition, Cac3p associates with Npr1p, a cytoplasmic kinase that stablizes several nutrient transporters by antagonizing a ubiquitin-mediated protein degradation pathway. Deletion of NPR1, like overexpression of Cac3p, suppressed the RAS/cAMP pathway. Furthermore, NPR1 overexpression interfered with the ability of CAC3 to suppress the RAS/cAMP pathway, indicating that extra Cac3p suppresses the RAS/cAMP pathway by sequestering Npr1p. Deletion of NPR1 did not affect the quantity, phosphorylation state, or localization of Ras2p. Consistent with the idea that Npr1p exerts its effect on the RAS/cAMP pathway by antagonizing a ubiquitin-mediated process, excess ubiquitin suppressed both the heat shock sensitivity and the sporulation defects caused by constitutive activation of the RAS/cAMP pathway. Thus, CAC3/MSI1 regulates the RAS/cAMP pathway via a chromatin-independent mechanism that involves the sequestration of Npr1p and may be due to the increased ubiquitination of an Npr1p substrate.

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