DeSUMOylation switches Kaiso from activator to repressor upon hyperosmotic stress.

Cell Death and Differentiation
Svetlana ZheniloEgor Prokhortchouk

Abstract

Kaiso is a member of the BTB/POZ zinc finger family, which is involved in cancer progression, cell cycle control, apoptosis, and WNT signaling. Depending on promoter context, it may function as either a transcriptional repressor or activator. Previous studies found that Kaiso might be SUMOylated due to heat shock, but the biological significance of Kaiso SUMOylation is unclear. Here, we find that K42 is the only amino acid within Kaiso that is modified with SUMO. Kaiso is monoSUMOylated at lysine 42 in cell lines of kidney origin under normal physiological conditions. SUMOylated Kaiso can activate transcription from exogenous methylated promoters, wherein the deSUMOylated form of the protein kept the ability to be a repressor. Rapid Kaiso deSUMOylation occurs in response to hyperosmotic stress and is reversible upon return to an isotonic environment. DeSUMOylation occurs within minutes in HEK293 cells treated with 100 mM NaCl and relaxes in 3 h even in a salt-containing medium. Genomic editing of Kaiso by conversion of K42 into R42 (K42R) in HEK293 cells that resulted in fully deSUMOylated endogenous protein led to misregulation of genes associated with ion transport, blood pressure, and the immune response. TRIM25 was signific...Continue Reading

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Citations

Jun 22, 2019·Biochemistry. Biokhimii︠a︡·D S KaplunS V Zhenilo
Oct 20, 2019·Journal of Molecular Biology·Amelia J HodgesBethany A Buck-Koehntop
Nov 13, 2018·Biochimica Et Biophysica Acta. Reviews on Cancer·Christina C PierreJuliet M Daniel
Apr 26, 2021·Doklady. Biochemistry and Biophysics·K Y KhalisovaA N Bonchuk
Jul 25, 2021·International Journal of Molecular Sciences·Darya KaplunSvetlana Zhenilo

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Datasets Mentioned

BETA
RFMEFI62114Х0010

Methods Mentioned

BETA
Assay
ChIP
PCR
transfection
ChIP-seq
immunoprecipitation

Software Mentioned

Kaiso
DESeq R
bedtools
DAVID

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