TY - JOUR
T1 - Cloning and chromosomal localization of the gene encoding human cyclin D-binding Myb-like protein (hDMP1)
AU - Bodner, Sara M.
AU - Naeve, Clayton W.
AU - Rakestraw, Karen M.
AU - Jones, Bart G.
AU - Valentine, Virginia A.
AU - Valentine, Marcus B.
AU - Luthardt, Frederick W.
AU - Willman, Cheryl L.
AU - Raimondi, Susana C.
AU - Downing, James R.
AU - Roussel, Martine F.
AU - Sherr, Charles J.
AU - Look, A. Thomas
N1 - Funding Information:
We thank Tom McNeil for assistance with sequence analysis, Sue Watson for editorial assistance, Doris Dodson for assistance with manuscript preparation, and the Tissue Resource Bank for supplying human tissues. This work was supported by National Cancer Institute grants CA 71907, CA 32102, and Cancer Center Core CA 21765, and by the American Lebanese Syrian Associated Charities (ALSAC), St. Jude Children's Research Hospital.
PY - 1999/3/18
Y1 - 1999/3/18
N2 - The murine transcription factor murine cyclin D-binding Myb-like protein (mDmp1) arrests the cell cycle in G1 phase, through an activity that can be overridden by direct interaction with the D-type cyclins. Here, we describe the identification, sequence, chromosomal localization, and expression of the human cognate, hDMP1. The hDMP1 cDNA contains a 2280 bp open reading frame that shares a high degree of identity with the mDmpI coding region. The 4.4 kb hDMP1 messenger RNA is ubiquitously expressed in normal human tissues, with highest levels in testis and substructures within the brain. By use of fluorescence in situ hybridization with a human genomic P1 probe, we assigned hDMP1 to chromosome 7, band q21. This chromosomal region is frequently deleted as part of the 7q-minus and monosomy 7 abnormalities of human acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We analyzed hDMP1 copy number by fluorescence in situ hybridization in leukemic blasts from nine patients with abnormalities of the long arm of chromosome 7, and in each case one allele of the hDMP1 gene was deleted. Functional analysis of the mDmp1 protein has shown that it negatively regulates cell proliferation, which suggests that this gene is a candidate suppressor of malignant transformation. Further study will be needed to determine whether gene- specific mutations implicate hDMP1 as a tumor suppressor in acute leukemias with deletions of the long arm of chromosome 7 or in other types of human malignancy.
AB - The murine transcription factor murine cyclin D-binding Myb-like protein (mDmp1) arrests the cell cycle in G1 phase, through an activity that can be overridden by direct interaction with the D-type cyclins. Here, we describe the identification, sequence, chromosomal localization, and expression of the human cognate, hDMP1. The hDMP1 cDNA contains a 2280 bp open reading frame that shares a high degree of identity with the mDmpI coding region. The 4.4 kb hDMP1 messenger RNA is ubiquitously expressed in normal human tissues, with highest levels in testis and substructures within the brain. By use of fluorescence in situ hybridization with a human genomic P1 probe, we assigned hDMP1 to chromosome 7, band q21. This chromosomal region is frequently deleted as part of the 7q-minus and monosomy 7 abnormalities of human acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We analyzed hDMP1 copy number by fluorescence in situ hybridization in leukemic blasts from nine patients with abnormalities of the long arm of chromosome 7, and in each case one allele of the hDMP1 gene was deleted. Functional analysis of the mDmp1 protein has shown that it negatively regulates cell proliferation, which suggests that this gene is a candidate suppressor of malignant transformation. Further study will be needed to determine whether gene- specific mutations implicate hDMP1 as a tumor suppressor in acute leukemias with deletions of the long arm of chromosome 7 or in other types of human malignancy.
KW - Cell cycle regulation
KW - Myelodysplastic syndrome
KW - Transcription factor
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U2 - 10.1016/S0378-1119(98)00591-5
DO - 10.1016/S0378-1119(98)00591-5
M3 - Article
C2 - 10095122
AN - SCOPUS:0033580429
SN - 0378-1119
VL - 229
SP - 223
EP - 228
JO - Gene
JF - Gene
IS - 1-2
ER -