The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-mediated growth

Ling Li, Sarah Anderson, Julie Secombe, Robert N. Eisenman

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The essential and highly conserved role of Myc in organismal growth and development is dependent on the control of Myc protein abundance. It is now well established that Myc levels are in part regulated by ubiquitin-dependent proteasomal degradation. Using a genetic screen for modifiers of Drosophila Myc (dMyc)-induced growth, we identified and characterized a ubiquitin-specific protease (USP), Puffyeye (Puf), as a novel regulator of dMyc levels and function in vivo. We show that puf genetically and physically interacts with dMyc and the ubiquitin ligase archipelago (ago) to modulate a dMyc-dependent cell growth phenotype, and that varying Puf levels in both the eye and wing phenocopies the effects of altered dMyc abundance. Puf containing point mutations within its USP enzymatic domain failed to alter dMyc levels and displayed no detectable phenotype, indicating the importance of deubiquitylating activity for Puf function. We find that dMyc induces Ago, indicating that dMyc triggers a negative-feedback pathway that is modulated by Puf. In addition to its effects on dMyc, Puf regulates both Ago and its cell cycle substrate Cyclin E. Therefore, Puf influences cell growth by controlling the stability of key regulatory proteins.

Original languageEnglish (US)
Pages (from-to)4776-4787
Number of pages12
JournalDevelopment (Cambridge)
Volume140
Issue number23
DOIs
StatePublished - Dec 1 2013

Fingerprint

Ubiquitin-Specific Proteases
Drosophila
Growth
Ubiquitin
Phenotype
Cyclin E
Ligases
Growth and Development
Point Mutation
Cell Cycle
Proteins

Keywords

  • Deubiquitinase
  • Drosophila
  • Growth
  • Myc
  • Protein degradation

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-mediated growth. / Li, Ling; Anderson, Sarah; Secombe, Julie; Eisenman, Robert N.

In: Development (Cambridge), Vol. 140, No. 23, 01.12.2013, p. 4776-4787.

Research output: Contribution to journalArticle

Li, Ling ; Anderson, Sarah ; Secombe, Julie ; Eisenman, Robert N. / The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-mediated growth. In: Development (Cambridge). 2013 ; Vol. 140, No. 23. pp. 4776-4787.
@article{bdf981de3248434a9339591bb0d2ade6,
title = "The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-mediated growth",
abstract = "The essential and highly conserved role of Myc in organismal growth and development is dependent on the control of Myc protein abundance. It is now well established that Myc levels are in part regulated by ubiquitin-dependent proteasomal degradation. Using a genetic screen for modifiers of Drosophila Myc (dMyc)-induced growth, we identified and characterized a ubiquitin-specific protease (USP), Puffyeye (Puf), as a novel regulator of dMyc levels and function in vivo. We show that puf genetically and physically interacts with dMyc and the ubiquitin ligase archipelago (ago) to modulate a dMyc-dependent cell growth phenotype, and that varying Puf levels in both the eye and wing phenocopies the effects of altered dMyc abundance. Puf containing point mutations within its USP enzymatic domain failed to alter dMyc levels and displayed no detectable phenotype, indicating the importance of deubiquitylating activity for Puf function. We find that dMyc induces Ago, indicating that dMyc triggers a negative-feedback pathway that is modulated by Puf. In addition to its effects on dMyc, Puf regulates both Ago and its cell cycle substrate Cyclin E. Therefore, Puf influences cell growth by controlling the stability of key regulatory proteins.",
keywords = "Deubiquitinase, Drosophila, Growth, Myc, Protein degradation",
author = "Ling Li and Sarah Anderson and Julie Secombe and Eisenman, {Robert N.}",
year = "2013",
month = "12",
day = "1",
doi = "10.1242/dev.096941",
language = "English (US)",
volume = "140",
pages = "4776--4787",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "23",

}

TY - JOUR

T1 - The Drosophila ubiquitin-specific protease Puffyeye regulates dMyc-mediated growth

AU - Li, Ling

AU - Anderson, Sarah

AU - Secombe, Julie

AU - Eisenman, Robert N.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - The essential and highly conserved role of Myc in organismal growth and development is dependent on the control of Myc protein abundance. It is now well established that Myc levels are in part regulated by ubiquitin-dependent proteasomal degradation. Using a genetic screen for modifiers of Drosophila Myc (dMyc)-induced growth, we identified and characterized a ubiquitin-specific protease (USP), Puffyeye (Puf), as a novel regulator of dMyc levels and function in vivo. We show that puf genetically and physically interacts with dMyc and the ubiquitin ligase archipelago (ago) to modulate a dMyc-dependent cell growth phenotype, and that varying Puf levels in both the eye and wing phenocopies the effects of altered dMyc abundance. Puf containing point mutations within its USP enzymatic domain failed to alter dMyc levels and displayed no detectable phenotype, indicating the importance of deubiquitylating activity for Puf function. We find that dMyc induces Ago, indicating that dMyc triggers a negative-feedback pathway that is modulated by Puf. In addition to its effects on dMyc, Puf regulates both Ago and its cell cycle substrate Cyclin E. Therefore, Puf influences cell growth by controlling the stability of key regulatory proteins.

AB - The essential and highly conserved role of Myc in organismal growth and development is dependent on the control of Myc protein abundance. It is now well established that Myc levels are in part regulated by ubiquitin-dependent proteasomal degradation. Using a genetic screen for modifiers of Drosophila Myc (dMyc)-induced growth, we identified and characterized a ubiquitin-specific protease (USP), Puffyeye (Puf), as a novel regulator of dMyc levels and function in vivo. We show that puf genetically and physically interacts with dMyc and the ubiquitin ligase archipelago (ago) to modulate a dMyc-dependent cell growth phenotype, and that varying Puf levels in both the eye and wing phenocopies the effects of altered dMyc abundance. Puf containing point mutations within its USP enzymatic domain failed to alter dMyc levels and displayed no detectable phenotype, indicating the importance of deubiquitylating activity for Puf function. We find that dMyc induces Ago, indicating that dMyc triggers a negative-feedback pathway that is modulated by Puf. In addition to its effects on dMyc, Puf regulates both Ago and its cell cycle substrate Cyclin E. Therefore, Puf influences cell growth by controlling the stability of key regulatory proteins.

KW - Deubiquitinase

KW - Drosophila

KW - Growth

KW - Myc

KW - Protein degradation

UR - http://www.scopus.com/inward/record.url?scp=84887903330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887903330&partnerID=8YFLogxK

U2 - 10.1242/dev.096941

DO - 10.1242/dev.096941

M3 - Article

C2 - 24173801

AN - SCOPUS:84887903330

VL - 140

SP - 4776

EP - 4787

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 23

ER -