Proteomics

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Cla4 catalyzed Set1 phosphorylation

ABSTRACT: H3K4me3 is catalyzed by the Set1/MLL family of methyltransferases, whose function in catalyzing H3K4me3 is unique. Impaired function of Set1/MLL family members can lead to many abnormalities, such as bone and nerve defects, leukemia, and even death. Although the Set1 family plays an important regulatory role in various biological processes, it is still unclear how the Set1 protein itself is regulated and how protein levels are maintained. Due to the numerous homologues, complex composition, and high molecular weight of Set1 in higher organisms, especially humans, related research is greatly limited. In brewing yeast, Set1 is the only methyltransferase that catalyzes H3K4me3 and is highly conserved between species. Therefore, yeast is an ideal model for studying the functions and mechanisms of the Set1 family. In addition, Set1 protein plays an important role in regulating gene transcription, promoting telomere silencing, and maintaining cell lifespan. The Set1 family also plays an important regulatory role in the occurrence and development of various cancers.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Yu Qi  

LAB HEAD: Yu qi

PROVIDER: PXD042010 | Pride | 2023-10-24

REPOSITORIES: Pride

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Publications

Cla4 phosphorylates histone methyltransferase Set1 to prevent its degradation by the APC/C<sup>Cdh1</sup> complex.

Gong Xuanyunjing X   Wang Shanshan S   Yu Qi Q   Wang Min M   Ge Feng F   Li Shanshan S   Yu Xilan X  

Science advances 20230929 39

H3K4 trimethylation (H3K4me3) is a conserved histone modification catalyzed by histone methyltransferase Set1, and its dysregulation is associated with pathologies. Here, we show that Set1 is intrinsically unstable and elucidate how its protein levels are controlled within cell cycle and during gene transcription. Specifically, Set1 contains a destruction box (D-box) that is recognized by E3 ligase APC/C<sup>Cdh1</sup> and degraded by the ubiquitin-proteasome pathway. Cla4 phosphorylates serine  ...[more]

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