Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias.

Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias.
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DOI:
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发表时间:
1995-03
期刊:
影响因子:
11.2
通讯作者:
J. Pietenpol;S. Bohlander;Y. Sato;N. Papadopoulos;Bo Liu;C. Friedman;B. Trask;James M. Roberts;K. Kinzler;J. Rowley;B. Vogelstein
J. Pietenpol;S. Bohlander;Y. Sato;N. Papadopoulos;Bo Liu;C. Friedman;B. Trask;James M. Roberts;K. Kinzler;J. Rowley;B. Vogelstein
中科院分区:
医学1区
文献类型:
--
作者:
J. Pietenpol;S. Bohlander;Y. Sato;N. Papadopoulos;Bo Liu;C. Friedman;B. Trask;James M. Roberts;K. Kinzler;J. Rowley;B. Vogelstein

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p27 Kip 1(p27)基因编码细胞周期蛋白依赖性激酶活性的诱导型抑制剂。使用小鼠p27 cDNA作为探针,我们获得了一个人的cDNA克隆,随后用它来分离该基因的基因组克隆。人p27基因的编码区包含在两个外显子中。p27的氨基酸序列和内含子-外显子结构与以前发现的相关细胞周期蛋白依赖性激酶抑制剂p21 Waf 1(p21)相似。结合体细胞杂交和荧光原位杂交分析,将p27基因定位于染色体12 p13带。p27基因产物被认为控制白细胞的细胞周期,并且已知12 p13染色体带在白血病中缺失,这表明p27基因可能在白血病中充当肿瘤抑制基因。虽然p27被发现驻留在血液恶性肿瘤的染色体丢失的最小区域中,但在白血病样品中未观察到p27突变。p27单倍不足可能赋予白血病细胞生长优势。
The p27Kip1 (p27) gene encodes an inducible inhibitor of cyclin-dependent kinase activity. Using a murine p27 cDNA as probe, we obtained a human cDNA clone and subsequently used it to isolate a genomic clone of this gene. The coding region of the human p27 gene was contained in two exons. Both the amino acid sequence and intron-exon organization of p27 were similar to those previously found for the related cyclin-dependent kinase inhibitor p21Waf1 (p21). The p27 gene was localized to chromosome band 12p13 by a combination of somatic cell hybrid and fluorescence in situ hybridization analyses. The p27 gene product is thought to control the leukocyte cell cycle and the 12p13 chromosomal band is known to be deleted in leukemias, suggesting that the p27 gene may act as a tumor suppressor gene in leukemias. Although p27 was found to reside in the minimal region of chromosomal loss in hematological malignancies, no mutations of p27 were observed in leukemia samples. Haploinsufficiency of p27 may confer a growth advantage to leukemia cells.