Cks1 activates transcription by binding to the ubiquitylated proteasome.
Cyclin-dependent kinase-associated protein 1 (Cks1) is involved in the control of the transcription of a subset of genes in addition to its role in controlling the cell cycle in the budding yeast Saccharomyces cerevisiae. By directly ligating Cks1 onto a GAL1 promoter-driven reporter, we demonstrated that Cks1 acts as a transcription activator. Using this method, we dissected the downstream events from Cks1 recruitment at the promoter. We showed that subsequent to promoter binding, Cdc28 binding is required to modulate the level of gene expression. The ubiquitin-binding domain of Cks1 is essential for implementing downstream transcription events, which appears to recruit the proteasome via ubiquitylated proteasome subunits. We propose that the selective ability of Cks1 to bind ubiquitin allows this small molecule the flexibility to bind large protein complexes with specificity and that this may represent a novel mechanism of regulating transcriptional activation.
Eukaryotic Chromatin Dynamics Group, MRC Clinical Sciences Centre, Imperial College Hammersmith Campus, London, United Kingdom.
Roman
R
Holic
Alexander
A
Kukalev
Sophie
S
Lane
Edward J
EJ
Andress
Ivy
I
Lau
Conny W H
CW
Yu
Mariola J
MJ
Edelmann
Benedikt M
BM
Kessler
Veronica P C C
VP
Yu
D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D017489:CDC28 Protein Kinase, S cerevisiae / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D004718:Saccharomycetales / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D025801:Ubiquitin; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae; D046988:Proteasome Endopeptidase Complex