PMID- 10490600
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 10
DP  - 1999 Oct
TI  - DOT4 links silencing and cell growth in Saccharomyces cerevisiae.
PG  - 6608-20
AB  - Transcriptional silencing in Saccharomyces cerevisiae occurs at specific loci and 
      is mediated by a multiprotein complex that includes Rap1p and the Sir proteins. 
      We studied the function of a recently identified gene, DOT4, that disrupts 
      silencing when overexpressed. DOT4 encodes an ubiquitin processing protease 
      (hydrolase) that is primarily located in the nucleus. By two-hybrid analysis, the 
      amino-terminal third of Dot4p interacts with the silencing protein Sir4p. Cells 
      lacking DOT4 exhibited reduced silencing and a corresponding decrease in the 
      level of Sir4p. Together, these findings suggest that Dot4p regulates silencing 
      by acting on Sir4p. In strains with several auxotrophic markers, loss of DOT4 
      ubiquitin hydrolase activity also results in a slow-growth defect. The defect can 
      be partially suppressed by mutations in a subunit of the 26S proteasome, 
      suggesting that Dot4p has the ability to prevent ubiquitin-mediated degradation. 
      Furthermore, wild-type SIR2, SIR3, and SIR4 are required for full manifestation 
      of the growth defect in a dot4 strain, indicating that the growth defect is 
      caused in part by a silencing-related mechanism. We propose that Dot4p helps to 
      restrict the location of silencing proteins to a limited set of genomic loci.
FAU - Kahana, A
AU  - Kahana A
AD  - Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, 
      Washington 98109, USA.
FAU - Gottschling, D E
AU  - Gottschling DE
LA  - eng
GR  - R01 GM043893/GM/NIGMS NIH HHS/United States
GR  - T32 GM007281/GM/NIGMS NIH HHS/United States
GR  - 5T32 GM07281/GM/NIGMS NIH HHS/United States
GR  - GM43893/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Fungal Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (SIR3 protein, S cerevisiae)
RN  - 0 (SIR4 protein, S cerevisiae)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - 0 (Silent Information Regulator Proteins, Saccharomyces cerevisiae)
RN  - 0 (Trans-Activators)
RN  - 0 (Ubiquitins)
RN  - EC 3.4.19.12 (UBP10 protein, S cerevisiae)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
RN  - EC 3.5.1.- (SIR2 protein, S cerevisiae)
RN  - EC 3.5.1.- (Sirtuin 2)
RN  - EC 3.5.1.- (Sirtuins)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Amino Acid Sequence
MH  - DNA-Binding Proteins/metabolism
MH  - Fungal Proteins/*metabolism
MH  - Gene Expression Regulation, Fungal
MH  - *Gene Silencing
MH  - *Histone Deacetylases
MH  - Molecular Sequence Data
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Peptide Fragments/metabolism
MH  - Protein Binding
MH  - *Protein Processing, Post-Translational
MH  - Saccharomyces cerevisiae/*genetics/growth & development
MH  - *Saccharomyces cerevisiae Proteins
MH  - *Silent Information Regulator Proteins, Saccharomyces cerevisiae
MH  - Sirtuin 2
MH  - Sirtuins
MH  - Trans-Activators/metabolism
MH  - Two-Hybrid System Techniques
MH  - Ubiquitin Thiolesterase
MH  - Ubiquitins/*metabolism
PMC - PMC84633
EDAT- 1999/09/22 00:00
MHDA- 1999/09/22 00:01
CRDT- 1999/09/22 00:00
PHST- 1999/09/22 00:00 [pubmed]
PHST- 1999/09/22 00:01 [medline]
PHST- 1999/09/22 00:00 [entrez]
AID - 0742 [pii]
AID - 10.1128/MCB.19.10.6608 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Oct;19(10):6608-20. doi: 10.1128/MCB.19.10.6608.