KLHL25 (15q25.3), ENC-2 . CUL3-adaptori ATP-sitraattilyaasin (ACLY) säätely

 https://www.ncbi.nlm.nih.gov/gene/?term=Homo+sapiens+KLHL25

Also known as ENC2; ENC-2

Expression Broad expression in brain (RPKM 6.7), testis (RPKM 5.6) and 23 other tissues See more

Orthologs mouse all

Preferred Names

kelch-like protein 25

Names

BTB/POZ KELCH domain protein

ectoderm-neural cortex protein 2

ectodermal-neural cortex 2

kelch-like 25

1. Evidence for shared genetic risk between methamphetamine-induced psychosis and schizophrenia. Ikeda M, et al. Neuropsychopharmacology, 2013 Sep. PMID 23594818, Free PMC Article
2. Translational homeostasis via the mRNA cap-binding protein, eIF4E. Yanagiya A, et al. Mol Cell, 2012 Jun 29. PMID 22578813, Free PMC Article  We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination.
3. Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Zhang C, et al. Genes Dev, 2016 Sep 1. PMID 27664236, AbstractIncreased lipid synthesis is a key characteristic of many cancers that is critical for cancer progression. ATP-citrate lyase (ACLY), a key enzyme for lipid synthesis, is frequently overexpressed or activated in cancer to promote lipid synthesis and tumor progression. Cullin3 (CUL3), a core protein for the CUL3-RING ubiquitin ligase complex, has been reported to be a tumor suppressor and frequently down-regulated in lung cancer. Here, we found that CUL3 interacts with ACLY through its adaptor protein, KLHL25 (Kelch-like family member 25), to ubiquitinate and degrade ACLY in cells. Through negative regulation of ACLY, CUL3 inhibits lipid synthesis, cell proliferation, and xenograft tumor growth of lung cancer cells. Furthermore, ACLY inhibitor SB-204990 greatly abolishes the promoting effect of CUL3 down-regulation on lipid synthesis, cell proliferation, and tumor growth. Importantly, low CUL3 expression is associated with high ACLY expression and poor prognosis in human lung cancer. In summary, our results identify CUL3-KLHL25 ubiquitin ligase as a novel negative regulator for ACLY and lipid synthesis and demonstrate that decreased CUL3 expression is an important mechanism for increased ACLY expression and lipid synthesis in lung cancer. These results also reveal that negative regulation of ACLY and lipid synthesis is a novel and critical mechanism for CUL3 in tumor suppression.
   
4. Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study. Lunetta KL, et al. BMC Med Genet, 2007 Sep 19. PMID 17903295, Free PMC Article
 ACLY

https://www.sciencedirect.com/science/article/pii/S0163782719300499
See all (23) citation
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See citations in PubMed for homologs of this gene provided by HomoloGene

 

     CDS             1..589
                     /gene="KLHL25"
                     /gene_synonym="ENC-2; ENC2"
                     /coded_by="NM_022480.4:171..1940"
                     /db_xref="CCDS:CCDS10339.1"
                     /db_xref="GeneID:64410"
                     /db_xref="HGNC:HGNC:25732"
ORIGIN      
        1 msvsvhetrk srsstgsmnv tlfhkashpd cvlahlntlr khcmftdvtl wagdrafpch
       61 ravlaassry feamfshglr esrddtvnfq dnlhpevlel lldfayssri aineenaesl
      121 leagdmlqfh dvrdaaaefl eknlfpsncl gmmllsdahq crrlyefswr mclvhfetvr
      181 qsedfnslsk dtlldlissd eletedervv feailqwvkh dleprkvhlp ellrsvrlal
      241 lpsdclqeav sseallmade rtklimdeal rcktrilqnd gvvtspcarp rkaghtllil
      301 ggqtfmcdki yqvdhkakei ipkadlpspr kefsasaigc kvyvtggrgs engvskdvwv
      361 ydtvheewsk aapmliarfg hgsaelencl yvvgghtsla gvfpaspsvs lkqvekydpg
      421 ankwmmvapl rdgvsnaavv saklklfvfg gtsihrdmvs kvqcydpsen rwtikaecpq
      481 pwrytaaavl gsqifimggd teftaasayr fdcetnqwtr igdmtakrms chalasgnkl
      541 yvvggyfgtq rcktldcydp tsdtwncitt vpysliptaf vstwkhlpa

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