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组蛋白去甲基化酶Kdm5在……中控制Hid诱导的细胞死亡。

The histone demethylase Kdm5 controls Hid-induced cell death in .

作者信息

Herz Hans-Martin, Bergmann Andreas

机构信息

St. Jude Children's Research Hospital, Department of Hematology, 262 Danny Thomas Place, Memphis, TN 38105.

UMass Chan Medical School, Department of Molecular, Cell and Cancer Biology, 364 Plantation Street, Worcester, MA 01605, USA.

出版信息

Front Cell Death. 2024;3. doi: 10.3389/fceld.2024.1471050. Epub 2024 Nov 19.

Abstract

We conducted an EMS mutagenesis screen on chromosome arm 2L to identify recessive suppressors of -induced apoptosis in the eye. Through this screen, we recovered three alleles of the lysine demethylase gene . Kdm5, a member of the JmjC-domain-containing protein family, possesses histone demethylase activity towards H3K4me3. Our data suggest that Kdm5 specifically regulates Hid-induced cell death during development, as we did not observe control of Reaper- or Grim-induced cell death by . Interestingly, -induced apoptosis is suppressed independently of Kdm5's demethylase activity. Our findings indicate that Rbf and dMyc are necessary for mosaics to suppress -induced cell death. Moreover, mosaics failed to suppress apoptosis induced by a mutant form of Hid that is resistant to inhibition by Erk-type MAPK activity. Additionally, dominantly enhances the wing phenotype of an activated MAPK mutant. These results collectively suggest that Kdm5 controls Hid-induced apoptosis by regulating the Rbf, dMyc, and MAPK pathways.

摘要

我们在2L染色体臂上进行了EMS诱变筛选,以鉴定眼睛中由hid诱导的细胞凋亡的隐性抑制因子。通过该筛选,我们获得了赖氨酸去甲基化酶基因的三个等位基因。Kdm5是含JmjC结构域蛋白家族的成员,对H3K4me3具有组蛋白去甲基化酶活性。我们的数据表明,Kdm5在发育过程中特异性调节Hid诱导的细胞死亡,因为我们没有观察到它对Reaper或Grim诱导的细胞死亡的调控。有趣的是,hid诱导的细胞凋亡被抑制,且与Kdm5的去甲基化酶活性无关。我们的研究结果表明,Rbf和dMyc对于抑制hid诱导的细胞死亡的镶嵌体是必需的。此外,镶嵌体无法抑制由对Erk型MAPK活性抑制具有抗性的Hid突变体诱导的细胞凋亡。此外,它显性增强了活化MAPK突变体的翅膀表型。这些结果共同表明,Kdm5通过调节Rbf、dMyc和MAPK途径来控制Hid诱导的细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4fb/12101616/b359a053055a/nihms-2082431-f0001.jpg

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