p53 expression in K562 cells is associated with caspase-mediated cleavage of c-ABL and BCR-ABL protein kinases

被引:29
作者
Di Bacco, AMA
Cotter, TG [1 ]
机构
[1] Univ Coll, Dept Biochem, Tumour Biol Lab, Cork, Ireland
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
关键词
K562; cells; differentiation; caspase; c-Abl/Bcr-Abl; p53;
D O I
10.1046/j.1365-2141.2002.03468.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The chimaeric BCR-ABL oncoprotein is the molecular hallmark of chronic myeloid leukaemia (CML). Expression of Bcr-Abl has been associated with arrested differentiation as well as resistance to apoptosis. The downstream pathway involved in apoptosis resistance has been extensively studied, whereas the role of Bcr-Abl in cell differentiation is largely unclear. A recent report has shown that Bcr-Abl expression alone is sufficient to increase the number of multipotent and myeloid lineage-committed progenitors in a dose-dependent manner while suppressing the development of committed erythroid progenitors. In accordance with this model, downregulation of c-Abl and Bcr-Abl has been observed during differentiation in different systems, although the mechanism is still largely unknown. To investigate the relationship between erythroid differentiation and c-Abl and Bcr-Abl levels, we induced differentiation in K562 cells using a temperature-inducible p53 mutant (p53Val1335). It was found that p53-induced erythroid differentiation in K562 cells required caspase activity. During this process, caspase-dependent cleavage of c-Abl and Bcr-Abl tyrosine kinases was observed, suggesting a new mechanism for the downregulation of the kinases during erythroid differentiation.
引用
收藏
页码:588 / 597
页数:10
相关论文
共 55 条
[21]   ABL ONCOGENE EXPRESSION DURING ERYTHROLEUKEMIA CELL-DIFFERENTIATION [J].
LEIBOWITZ, D ;
POPENOE, D ;
MEARS, JG ;
BANK, A ;
SCHAEFERREGO, K .
LEUKEMIA RESEARCH, 1991, 15 (01) :65-70
[22]   Integrins regulate the association and phosphorylation of paxillin by c-Abl [J].
Lewis, JM ;
Schwartz, MA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (23) :14225-14230
[23]   Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear transport [J].
Lewis, JM ;
Baskaran, R ;
Taagepera, S ;
Schwartz, MA ;
Wang, JYJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (26) :15174-15179
[24]   Transcriptional activation of the human p21(WAF1/CIP1) gene by retinoic acid receptor - Correlation with retinoid induction of U937 cell differentiation [J].
Liu, M ;
Iavarone, A ;
Freedman, LP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (49) :31723-31728
[25]   HUMAN CHRONIC MYELOGENOUS LEUKEMIA CELL-LINE WITH POSITIVE PHILADELPHIA CHROMOSOME [J].
LOZZIO, CB ;
LOZZIO, BB .
BLOOD, 1975, 45 (03) :321-334
[26]   CONDITIONAL INHIBITION OF TRANSFORMATION AND OF CELL-PROLIFERATION BY A TEMPERATURE-SENSITIVE MUTANT OF P53 [J].
MICHALOVITZ, D ;
HALEVY, O ;
OREN, M .
CELL, 1990, 62 (04) :671-680
[27]   THE CYTOGENETIC SCENARIO OF CHRONIC MYELOID-LEUKEMIA [J].
MITELMAN, F .
LEUKEMIA & LYMPHOMA, 1993, 11 :11-15
[28]  
Morgan SE, 1997, ADV CANCER RES, V71, P1, DOI 10.1016/S0065-230X(08)60095-0
[29]   REGULATION OF BIOSYNTHESIS AND PHOSPHORYLATION OF P210BCR ABL PROTEIN DURING DIFFERENTIATION INDUCTION OF K-562 CELLS [J].
NISHIMURA, J ;
TAKAHIRA, H ;
SHIBATA, K ;
MUTA, K ;
YAMAMOTO, M ;
IDEGUCHI, H ;
UMEMURA, T ;
NAWATA, H .
LEUKEMIA RESEARCH, 1988, 12 (11-12) :875-&
[30]  
NOWELL PETER C., 1966, SEMINARS HEMATOL, V3, P114