ZBTB33 (X ) , Znf-Kaiso, ZNF348. Hyperosmoottisuuden ja isotonisuuden sensorijärjjestelmää

https://www.ncbi.nlm.nih.gov/gene/10009

ZBTB33 zinc finger and BTB domain containing 33 [ Homo sapiens (human) ]

Gene ID: 10009, updated on 5-Apr-2020

Official Symbol

ZBTB33provided by HGNC

Official Full Name

zinc finger and BTB domain containing 33provided by HGNC

Also known as

ZNF348; ZNF-kaiso

Summary

This gene encodes a transcriptional regulator with bimodal DNA-binding specificity, which binds to methylated CGCG and also to the non-methylated consensus KAISO-binding site TCCTGCNA. The protein contains an N-terminal POZ/BTB domain and 3 C-terminal zinc finger motifs. It recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. It may contribute to the repression of target genes of the Wnt signaling pathway, and may also activate transcription of a subset of target genes by the recruitment of catenin delta-2 (CTNND2). Its interaction with catenin delta-1 (CTNND1) inhibits binding to both methylated and non-methylated DNA. It also interacts directly with the nuclear import receptor Importin-  (also known as karyopherin alpha2 or RAG cohort 1), which may mediate nuclear import of this protein. Alternatively spliced transcript variants encoding the same protein have been identified.[provided by RefSeq, May 2010]

Expression

Ubiquitous expression in skin (RPKM 10.2), bone marrow (RPKM 8.2) and 25 other tissues See more

Orthologs mouse all

Preferred Names

transcriptional regulator Kaiso

Names

WUGSC:H_DJ525N14.1

kaiso transcription factor

zinc finger and BTB domain-containing protein 33

1. Temporal and differential regulation of KAISO-controlled transcription by phosphorylated and acetylated p53 highlights a crucial regulatory role of apoptosis. Choi SH, et al. J Biol Chem, 2019 Aug 30. PMID 31296660,
2. CH···O Hydrogen Bonds Mediate Highly Specific Recognition of Methylated CpG Sites by the Zinc Finger Protein Kaiso. Nikolova EN, et al. Biochemistry, 2018 Apr 10. PMID 29546986, Free PMC Article
3. DeSUMOylation switches Kaiso from activator to repressor upon hyperosmotic stress. Zhenilo S, et al. Cell Death Differ, 2018 Nov. PMID 29472715, Free PMC Articl 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 significantly repressed in two K42R HEK293 clones. By a series of rescue experiments with K42R and KO HEK293 cells, we show that TRIM25 is a direct transcriptional target for Kaiso. In the absence of Kaiso, the level of TRIM25 is insensitive to hyperosmotic stress. Extending our observations to animal models, we show that in response to a high salt diet, Kaiso knockout mice are characterized by significantly higher blood pressure increases when compared to wild-type animals. Thus, we propose a novel biological role for Kaiso in the regulation of homeostasis.
4. Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women. Bassey-Archibong BI, et al. Cancer Causes Control, 2017 Nov. PMID 28887687, Free PMC Article
5. Loss of Kaiso expression in breast cancer cells prevents intra-vascular invasion in the lung and secondary metastasis. Kwiecien JM, et al. PLoS One, 2017. PMID 28880889, Free PMC Article

What's a GeneRIF?

1. The critical apoptosis regulator KAISO is a p53 target gene that is differently regulated by phosphorylated p53 or acetylated p53, depending on DNA damage responses stage.
2. Kaiso plays a role in regulating intestinal epithelial cell integrity and function
3. Kaiso modifies MTG16-driven inflammation and tumorigenesis; this suggests that Kaiso deregulation contributes to MTG16-dependent colitis and Colitis-associated carcinoma phenotypes.
4. EGFR-Kaiso signaling axis is a critical regulator of the miR-200-ZEB1 feedback loop promoting epithelial to mesenchymal transition and metastasis in prostate cancer.
5. 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.
6. that Kaiso can inhibit endothelial apoptosis via differentially regulating expression of BCL2, BAX, and BIK and that methylated DNA and specific Kaiso binding site (KBS) contribute to the gene regulatory activity of Kaiso.
7. The level of miR-4262 was found to be significantly decreased in CC tissues and cell lines. Moreover, decreased expression of miR-4262 was closely related to increased expression of Kaiso (ZBTB33).
8. extracellular microenvironment signals regulate RhoH and Kaiso to modulate actin-cytoskeleton structure and transcriptional activity during T cell migration
9. Kaiso silencing had similar effects as miR-181a overexpression in glioma cells, whereas overexpression of Kaiso in glioma cells partially reversed the inhibitory effects of the miR-181a mimic.
10. data show that Kaiso favors an mCpG over a CpG site by 2 orders of magnitude in affinity and that an important component of this effect is the presence of hydrophobic and CH...O contacts involving E535.