Mutations in S-adenosylhomocysteine hydrolase (AHCY) affect its nucleocytoplasmic distribution and capability to interact with S- adenosylhomocysteine hydrolase-like 1 protein (CROSBI ID 244483)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Grbeša, Ivana ; Kalo, Alon ; Belužić, Robert ; Kovačević, Lucija ; Lepur, Adriana ; Rokić, Filip ; Hochberg, Hodaya ; Kanter, Itamar ; Simunović, Vesna ; Muńoz-Torres, Pau Marc ; Shav-Tal, Yaron ; Vugrek, Oliver
engleski
Mutations in S-adenosylhomocysteine hydrolase (AHCY) affect its nucleocytoplasmic distribution and capability to interact with S- adenosylhomocysteine hydrolase-like 1 protein
S-adenosylhomocysteine hydrolase (AHCY) is thought to be located at the sites of ongoing AdoMet-dependent methylation, presumably in the cell nucleus. Endogenous AHCY is located both in cytoplasm and the nucleus. Little is known regarding mechanisms that drive its subcellular distribution, and even less is known on how mutations causing AHCY deficiency affect its intracellular dynamics. Using fluorescence microscopy and GFP-tagged AHCY constructs we show significant differences in the intensity ratio between nuclei and cytoplasm for mutant proteins when compared with wild type AHCY. Interestingly, nuclear export of AHCY is not affected by leptomycin B. Systematic deletions showed that AHCY has two regions, located at both sides of the protein, that contribute to its nuclear localization, implying the interaction with various proteins. In order to evaluate protein interactions in vivo we engaged in bimolecular fluorescence complementation (BiFC) based studies. We investigated previously assumed interaction with AHCY-like-1 protein (AHCYL1), a paralog of AHCY. Indeed, significant interaction between both proteins exists. Additionally, silencing AHCYL1 leads to moderate inhibition of nuclear export of endogenous AHCY.
AHCYAHCYL1 (IRBIT)BiFCLMB1NESNuclear export
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
nije evidentirano
Podaci o izdanju
96 (6)
2017.
579-590
objavljeno
0171-9335
1618-1298
10.1016/j.ejcb.2017.05.002
Povezanost rada
Biologija, Temeljne medicinske znanosti