TY - JOUR
T1 - The PEBP2β/CBFβ-SMMHC chimeric protein is localized both in the cell membrane and nuclear subfractions of leukemic cells carrying chromosomal inversion 16
AU - Kanto, S.
AU - Chiba, N.
AU - Tanaka, Y.
AU - Fujita, S.
AU - Endo, M.
AU - Kamada, N.
AU - Yoshikawa, K.
AU - Fukuzaki, A.
AU - Orikasa, S.
AU - Watanabe, T.
AU - Satake, M.
N1 - Funding Information:
We thank T Suzuki for technical advice on immunofluorescence and Ms I Imamura and Ms A Yao for secretarial assistance. This work was supported in part by research grants from the Ministry of Education, Science, Sports and Culture and the Ministry of Health and Welfare of Japan.
PY - 2000
Y1 - 2000
N2 - The chromosomal inversion (16)(p13q22), which is associated with the M4-eosinophilia subtype of human acute myeloid leukemia, causes the fusion of two distinct genes. The polypeptide encoded by the chimeric gene, PEBP2β/CBFβ-SMMHC, retains the ability to interact with, and dominantly interfere with the function of proteins possessing the Runt homology domain. The Runt protein homologs constitute the DNA binding subunit of the PEBP2/CBF transcription factor. We examined the sub-cellular localization of PEBP2β/CBFβ-SMMHC, as well as that of Runt protein homologs in leukemic cells carrying inversion 16 by immunoblot analysis. A significant amount of the PEBP2β/CBFβ-SMMHC protein was recovered from the nuclear fraction along with the Runt protein homologs. Furthermore, some of both polypeptides was retained in the DNA pellet that represents the material remaining after extraction of nuclear fraction with high salt. These observations suggest that the so-called dominant interfering effect of PEBP2β/CBFβ-SMMHC on PEBP2/CBF occurs inside the nucleus. In addition, we could detect PEBP2β/CBFβ-SMMHC in the cytoplasmic membrane fraction as well. The function of this membrane-located PEBP2β/CBFβ-SMMHC, if any, appears to be unrelated to that of Runt protein homologs.
AB - The chromosomal inversion (16)(p13q22), which is associated with the M4-eosinophilia subtype of human acute myeloid leukemia, causes the fusion of two distinct genes. The polypeptide encoded by the chimeric gene, PEBP2β/CBFβ-SMMHC, retains the ability to interact with, and dominantly interfere with the function of proteins possessing the Runt homology domain. The Runt protein homologs constitute the DNA binding subunit of the PEBP2/CBF transcription factor. We examined the sub-cellular localization of PEBP2β/CBFβ-SMMHC, as well as that of Runt protein homologs in leukemic cells carrying inversion 16 by immunoblot analysis. A significant amount of the PEBP2β/CBFβ-SMMHC protein was recovered from the nuclear fraction along with the Runt protein homologs. Furthermore, some of both polypeptides was retained in the DNA pellet that represents the material remaining after extraction of nuclear fraction with high salt. These observations suggest that the so-called dominant interfering effect of PEBP2β/CBFβ-SMMHC on PEBP2/CBF occurs inside the nucleus. In addition, we could detect PEBP2β/CBFβ-SMMHC in the cytoplasmic membrane fraction as well. The function of this membrane-located PEBP2β/CBFβ-SMMHC, if any, appears to be unrelated to that of Runt protein homologs.
KW - Acute myeloid leukemia
KW - Chimeric gene
KW - Immunoblot analysis
KW - PEBP2β/CBFβ
KW - Transcription factor
UR - http://www.scopus.com/inward/record.url?scp=0033623914&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033623914&partnerID=8YFLogxK
U2 - 10.1038/sj.leu.2401821
DO - 10.1038/sj.leu.2401821
M3 - Article
C2 - 10914550
AN - SCOPUS:0033623914
SN - 0887-6924
VL - 14
SP - 1253
EP - 1259
JO - Leukemia
JF - Leukemia
IS - 7
ER -
