Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements.
Fusion genes encoding the 3' part of the can gene are implicated in two types of leukemia. The dek-can fusion gene is present in t(6;9) acute myeloid leukemia and the set-can fusion gene is present in one case of acute undifferentiated leukemia. In order to obtain leads towards the molecular basis of these diseases, we have studied the cellular localization of the DEK-CAN and SET-CAN fusion proteins and their normal counterparts. DEK-CAN and SET-CAN were localized exclusively in the nucleus, and also DEK and SET were found to be nuclear proteins. However, CAN was mainly located at the nuclear and cytoplasmic face of the nuclear envelope. This observation is in accordance with the presence of an amino acid repeat in the C-terminal part of CAN, common to the family of nucleoporins. The C-terminal part also contains a nuclear location domain as shown by deletion analysis. This domain may be important for the presence of CAN at the nucleoplasmic side of the nuclear envelope. The relocation of the carboxyterminal part of CAN due to DEK-CAN and SET-CAN may reinforce a nuclear function of the CAN protein.
Fornerod
M
M
Department of Genetics, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Boer
J
J
van Baal
S
S
Jaeglé
M
M
von Lindern
M
M
Murti
K G
KG
Davis
D
D
Bonten
J
J
Buijs
A
A
Grosveld
G
G
D000208:Acute Disease; D001483:Base Sequence; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D004268:DNA-Binding Proteins; D005455:Fluorescent Antibody Technique; D056488:Histone Chaperones; D006801:Humans; D007150:Immunohistochemistry; D007938:Leukemia / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D014157:Transcription Factors; D014178:Translocation, Genetic
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C084738:DEK protein, human; D056488:Histone Chaperones; C085914:NUP214 protein, human; D009363:Neoplasm Proteins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D015513:Oncogene Proteins; D010750:Phosphoproteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; C513473:SET protein, human; D014157:Transcription Factors