KCTD21(11q14.1), KCASH2 ( KCTD sisältävä CUL3 adaptori, Hedgehog suppressori 2)

https://www.ncbi.nlm.nih.gov/gene/283219

Official Symbol

KCTD21

Official Full Name

potassium channel tetramerization domain containing 21

Also known as

KCASH2

Expression

Ubiquitous expression in thyroid (RPKM 3.5), brain (RPKM 3.4) and 25 other tissues See more

1. NM_001029859.3 → NP_001025030.1  BTB/POZ domain-containing protein KCTD21
   
   
   

   Conserved Domains (1) summary

   cd18395
   Location:3 → 100

   BTB_POZ_KCTD21; BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in potassium channel tetramerization domain-containing protein 21 (KCTD21)

1. Identification and characterization of KCASH2 and KCASH3, 2 novel Cullin3 adaptors suppressing histone deacetylase (HDAC)  and Hedgehog (Hh) activity in medulloblastoma. De Smaele E, et al. Neoplasia, 2011 Apr. PMID 21472142, Free PMC Article Abstract
   Medulloblastoma is the most common pediatric malignant brain tumor, arising from aberrant cerebellar precursors' development, a process mainly controlled by Hedgehog (Hh) signaling pathway. Histone deacetylase HDAC1 has been recently shown to modulate Hh signaling, deacetylating its effectors Gli1/2 and enhancing their transcriptional activity. Therefore, HDAC may represent a potential therapeutic target for Hh-dependent tumors, but still little information is available on the physiological mechanisms of HDAC regulation. The putative tumor suppressor REN(KCTD11) acts through ubiquitination-dependent degradation of HDAC1, thereby affecting Hh activity and medulloblastoma growth. We identify and characterize here two REN(KCTD11) homologues, defining a new family of proteins named KCASH, as "KCTD containing, Cullin3 adaptor, suppressor of Hedgehog." Indeed, the novel genes (KCASH2(KCTD21) and KCASH3(KCTD6)) share with REN(KCTD11) a number of features, such as a BTB domain required for the formation of a Cullin3 ubiquitin ligase complex and HDAC1 ubiquitination and degradation capability, suppressing the acetylation-dependent Hh/Gli signaling. Expression of KCASH2 and -3 is observed in cerebellum, whereas epigenetic silencing and allelic deletion are observed in human medulloblastoma. Rescuing KCASHs expression reduces the Hedgehog-dependent medulloblastoma growth, suggesting that loss of members of this novel family of native HDAC inhibitors is crucial in sustaining Hh pathway-mediated tumorigenesis. Accordingly, they might represent a promising class of endogenous "agents" through which this pathway may be targeted.
2. Cullin-3-KCTD10-mediated CEP97 degradation promotes primary cilium formation. Nagai T, et al. J Cell Sci, 2018 Dec 12. PMID 30404837
3. Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Bennett EJ, et al. Cell, 2010 Dec 10. PMID 21145461, Free PMC Article
4. The BioPlex Network: A Systematic Exploration of the Human Interactome. Huttlin EL, et al. Cell, 2015 Jul 16. PMID 26186194, Free PMC Article
5. Complete sequencing and characterization of 21,243 full-length human cDNAs. Ota T, et al. Nat Genet, 2004 Jan. PMID 14702039

See all (8) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

What's a GeneRIF?
  Rescuing KCASHs expression reduces the Hedgehog-dependent medulloblastoma growth, suggesting that loss of members of this novel family of native HDAC inhibitors is crucial in sustaining Hh pathway-mediated tumorigenesis.