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Nuclear Relocation of Normal Huntingtin
Author(s) -
Tao Tao,
Tartakoff Alan M.
Publication year - 2001
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1034/j.1600-0854.2001.002006385.x
Subject(s) - huntingtin , nucleoplasm , microbiology and biotechnology , biology , nucleus , huntingtin protein , nucleolus , nuclear protein , nuclear transport , endosome , cleavage (geology) , mutant , cell nucleus , genetics , intracellular , gene , transcription factor , paleontology , fracture (geology)
In Huntington's Disease (HD), the huntingtin protein (Htt) includes an expanded polyglutamine domain. Since mutant Htt concentrates in the nucleus of affected neurons, we have inquired whether normal Htt (Q 16−23 ) is also able to access the nucleus. We observe that a major pool of normal full‐length Htt of HeLa cells is anchored to endosomes and also detect RNase‐sensitive nuclear foci which include a 70‐kDa N‐terminal Htt fragment. Agents which damage DNA trigger caspase‐3‐dependent cleavage of Htt and dramatically relocate the 70 kDa fragment to the nucleoplasm. Considering that polyglutamine tracts stimulate caspase activation, mutant Htt is therefore poised to enter the nucleus. These considerations help rationalize the nuclear accumulation of Htt which is characteristic of HD and provide a first example of involvement of caspase cleavage in release of membrane‐bound proteins which subsequently enter the nucleus.