A FANCD2 domain activates Tip60-dependent apoptosis.
The FA (Fanconi anaemia) FANCD2 protein is pivotal in the cellular response to DNA interstrand cross-links. Establishing cells expressing exogenous FANCD2 has proven to be difficult compared with other DNA repair genes. We find that in transformed normal human fibroblasts, exogenous nuclear expression of FANCD2 induces apoptosis, dependent specifically on exons 10-13. This is the same region required for interaction with the histone acetyltransferase, Tip60. Deletion of exons 10-13 from FANCD2 N-terminal constructs (nucleotides 1-1100) eliminates the binary interaction with Tip60 and the cellular apoptotic response; moreover, cells can stably express FANCD2 at high levels if Tip60 is depleted. The results indicate that FANCD2-sponsored apoptosis requires an interaction with Tip60 and depends on Tip60.
Hejna
James
J
Department of Molecular and Medical Genetics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
Bruun
Donald
D
Pauw
Daniel
D
Moses
Robb E
RE
D017209:Apoptosis; D002467:Cell Nucleus / Q000378:metabolism; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000737:chemistry* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D005453:Fluorescence; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D019913:Nuclear Localization Signals / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
D052236:Fanconi Anemia Complementation Group D2 Protein; D019913:Nuclear Localization Signals; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5