Abstract
PML/RARA is the oncoprotein driving acute promyelocytic leukemia (APL). It suppresses genes expression by recruitment of a number of transcriptional repressors, resulting in differentiation block and malignant transformation of hematopoietic cells. Here, we found that mice primary hematopoietic progenitor cells (HPCs), transduced by DNA-binding-defective PML/RARA mutants, were deficient in colony formation. Further experiments showed that DNA-binding-defective PML/RARA mutants could not repress the transcription of retinoic acid regulated genes. Intriguingly, there were no significant differences of the micro-speckled intracellular distribution between the mutants and wild-type PML/RARA. Some retinoic acid target genes regulated by PML/RARA are involved in not only differentiation block but also hematopoietic cell self-renewal. Altogether, our data demonstrate that direct DNA-binding is essential for PML/RARA to immortalize hematopoietic cells, while disruption of PML-nuclear body does not seem to be a prerequisite for hematopoietic cell transformation.
MeSH 主题词
Animals
Cell Line
Cell Transformation, Neoplastic/genetics,metabolism,pathology
Cells, Cultured
DNA/metabolism
Gene Expression Regulation, Leukemic
Hematopoietic Stem Cells/metabolism,pathology
Leukemia, Promyelocytic, Acute/genetics,metabolism,pathology
Mice
Mice, Inbred C57BL
Mutation
Nuclear Proteins/genetics,metabolism
Oncogene Proteins, Fusion/genetics,metabolism
Promyelocytic Leukemia Protein
Receptors, Retinoic Acid/genetics,metabolism
Retinoic Acid Receptor alpha
Transcription Factors/genetics,metabolism
Tretinoin/metabolism
Tumor Suppressor Proteins/genetics,metabolism
化学物质
Nuclear Proteins
Oncogene Proteins, Fusion
Pml protein, mouse
Promyelocytic Leukemia Protein
Rara protein, mouse
Receptors, Retinoic Acid
Retinoic Acid Receptor alpha
Transcription Factors
Tumor Suppressor Proteins
Tretinoin
DNA
作者与单位
共 8 位作者，点击展开单位 / ORCID
Liu Xi
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yuan Hao
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Peres Laurent
Université de Paris 7/INSERM/CNRS UMR 944/7151, Equipe Labellisée No. 11 Ligue Nationale Contre le Cancer, Hôpital St. Louis, Paris, France.
Chen Saijuan
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chen Zhu
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
de The Hugues
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Université de Paris 7/INSERM/CNRS UMR 944/7151, Equipe Labellisée No. 11 Ligue Nationale Contre le Cancer, Hôpital St. Louis, Paris, France.
Zhou Jun
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhu Jun
CNRS-LIA124, Sino-French Research Center for Life Sciences and Genomics, State Key Laboratory of Medical Genomics, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Université de Paris 7/INSERM/CNRS UMR 944/7151, Equipe Labellisée No. 11 Ligue Nationale Contre le Cancer, Hôpital St. Louis, Paris, France.
