Hsk1- and SCF(Pof3)-dependent proteolysis of S. pombe Ams2 ensures histone homeostasis and centromere function.
Schizosaccharomyces pombe GATA factor Ams2 is responsible for cell cycle-dependent transcriptional activation of all the core histone genes peaking at G1/S phase. Intriguingly, its own protein level also fluctuates concurrently. Here, we show that Ams2 is ubiquitylated and degraded through the SCF (Skp1-Cdc53/Cullin-1-F-box) ubiquitin ligase, in which F box protein Pof3 binds this protein. Ams2 is phosphorylated at multiple sites, which is required for SCF(Pof3)-dependent proteolysis. Hsk1/Cdc7 kinase physically associates with and phosphorylates Ams2. Even mild overexpression of Ams2 induces constitutive histone expression and chromosome instability, and its toxicity is exaggerated when Hsk1 function is compromised. This is partly attributable to abnormal incorporation of canonical H3 into the central CENP-A/Cnp1-rich centromere, thereby reversing specific chromatin structures to apparently normal nucleosomes. We propose that Hsk1 plays a vital role during post S phase in genome stability via SCF(Pof3)-mediated degradation of Ams2, thereby maintaining centromere integrity.
Takayama
Yuko
Y
Institute of Life Science, Kurume University, Fukuoka 839-0864, Japan. yutakaya@lsi.kurume-u.ac.jp
Mamnun
Yasmine M
YM
Trickey
Michelle
M
Dhut
Susheela
S
Masuda
Fumie
F
Yamano
Hiroyuki
H
Toda
Takashi
T
Saitoh
Shigeaki
S
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism; D043171:Chromosomal Instability; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005800:Genes, Fungal; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D016196:S Phase / Q000235:genetics / Q000502:physiology; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
C472167:Ams2 protein, S pombe; D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D050980:GATA Transcription Factors; D006657:Histones; C514993:Pof3 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C094761:HSK1 protein, S pombe; D017346:Protein Serine-Threonine Kinases