Psychiatry related information on KLF8

• Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation [1].

Disease relevance of KLF8

• This work identifies KLF8 as a novel EMT-regulating transcription factor that opens a new avenue in EMT research and suggests an important role for KLF8 in human breast cancer invasion and metastasis [2].
• Taken together, our data suggest that FAK induces KLF8 expression in human ovarian cancer cells by activating the PI3K-Akt signaling pathway, leading to the activation of KLF8 promoter by Sp1 [3].

High impact information on KLF8

• Overexpression of KLF8 increases cell cycle progression, whereas inhibition of endogenous KLF8 by siRNA reduces it [4].
• In addition, site-directed mutagenesis identified lysine 67 as the major sumoylation site on KLF8 [5].
• In addition, the KLF8-enhanced transformation in the v-Src cells was prevented by ablating cyclin D1 expression [6].
• We have previously demonstrated that KLF8 mediates cell cycle progression downstream of focal adhesion kinase (FAK) by upregulating cyclin D1 [6].
• In contrast, expression of a dominant-negative mutant of KLF8 dramatically suppresses the transformed phenotypes induced by v-Src [6].

Biological context of KLF8

• These results establish KLF8 as a CACCC-box binding protein that associates with CtBP and represses transcription [7].
• We demonstrate that the zinc fingers of KLF8 recognize CACCC elements in DNA and that full-length KLF8 can repress a CACCC-dependent promoter [7].
• Mutation screening of probands from 20 unrelated XLMR families linked to the proximal short arm of the human X chromosome failed to show any mutation in the coding region of the KLF8 gene [1].
• We have mapped the X chromosome breakpoint to a 21 kb DNA fragment upstream of the first exon of the KLF8 (ZNF741) gene in Xp11.21 [1].
• YAC-derived cosmids were used to clone and map the IP1 breakpoints to a 180-kb interval that was flanked by DNA markers DXS705 and DXS741 [8].

Anatomical context of KLF8

• In co-transfection assays in K562 cells, it was demonstrated that KLF2, 5 and 13 positively regulate, and KLF8 negatively regulates, the gamma-globin gene through the CACCC promoter element [9].

Associations of KLF8 with chemical compounds

• Lysine 67 to arginine mutation strongly enhanced activity of KLF8 as a repressor or activator to its physiological target promoters and as an inducer of the G(1) cell cycle progression [5].

References