| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :1.1282196 |
| Hoxa 9 , Meis 1 and Pbx 1 proteins have been shown to physically interact with each other , as Hoxa 9 cooperatively binds consensus DNA sequences with Meis 1 and with Pbx 1 , while Meis 1 and Pbx 1 form heterodimers in both the presence and absence of DNA . 1.1282196^^^ |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.51662075 |
| Taken together , these data suggest that in myeloid leukemia cells MEIS 1 forms trimeric complexes with PBX and HOXA 9 , which in turn can bind to consensus PBX HOXA 9 DNA targets . . 0.51662075^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Using this approach , we identify three genes whose expression is activated by proviral integration in BXH 2 leukaemias ; Hoxa 7 , Hoxa 9 , and a Pbx 1 related homeobox gene , Meis 1 . ^^^ Proviral activation of Hoxa 7 or Hoxa 9 is strongly correlated with proviral activation of Meis 1 implying that Hoxa 7 and Hoxa 9 cooperate with Meis 1 in leukaemia formation . ^^^ |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| The expression of Meis 1 ( a novel Pbx related homeobox gene ) and either Hoxa 7 or Hoxa 9 are coactivated by retroviral integration in BXH 2 murine myeloid leukemias ( T Nakamura , DA Largaespada , JD Shaughnessy Jr , NA Jenkins and NG Copeland ( 1996 ) Nature Genet . 12 : 149 153 ) . ^^^ As Pbx proteins are Hox cofactors , which cooperatively bind DNA with Hox proteins to modulate the otherwise similar DNA bind specificities of Hox proteins , these results suggested that Meis 1 may function as a cofactor for Hoxa 7 and Hoxa 9 in the induction of murine myeloid leukemias . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Most human myeloid leukemia cell lines co expressed MEIS 1 with HOXA 7 and HOXA 9 . ^^^ |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| We have previously shown that HOXA 9 collaborates with MEIS 1 in the induction of acute myeloid leukemia ( AML ) . ^^^ In this report , we demonstrate that HOXB 3 , which is highly divergent from HOXA 9 , also genetically interacts with MEIS 1 , but not with PBX 1 , in generating AML . ^^^ In addition , we show that the HOXA 9 and HOXB 3 genes play key roles in establishing all the main characteristics of the leukemias , while MEIS 1 functions only to accelerate the onset of the leukemic transformation . ^^^ Contrasting the reported functional similarities between PREP 1 and MEIS 1 , such as PBX nuclear retention , we also show that PREP 1 overexpression is incapable of accelerating the HOXA 9 induced AML , suggesting that MEIS 1 function in transformation must entail more than PBX nuclear localization . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| The co expression of NUP 98 HOXA9 and Meis 1 accelerated the transformation of MPD to AML , identifying a genetic interaction previously observed for Hoxa 9 and Meis 1 . ^^^ |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| The MEIS 1 homeobox protein forms a complex with the HOXA 9 and PBX proteins that are implicated in human leukemia . ^^^ |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| We now show that the Hoxa 9 protein physically interacts with Meis 1 proteins by forming heterodimeric binding complexes on a DNA target containing a Meis 1 site ( TGACAG ) and an AbdB like Hox site ( TTTTACGAC ) . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Frequent co expression of the HOXA 9 and MEIS 1 homeobox genes in human myeloid leukemias . ^^^ Recent studies have demonstrated that enforced co expression of HOXA 9 and MEIS 1 in murine marrow leads to rapid development of myeloid leukemia , and that these proteins exhibit cooperative DNA binding . ^^^ We surveyed expression of HOXA 9 and MEIS 1 in 24 leukemic cell lines and 80 patient samples , using RNase protection analyses and immunohistochemistry . ^^^ We demonstrate that the expression of HOXA 9 and MEIS 1 in leukemia cells is uniquely myeloid , and that these genes are commonly co expressed in myeloid cell lines and in samples of acute myelogenous leukemia ( AML ) of all subtypes except in promyelocytic leukemia . ^^^ While HOXA 9 is expressed in most cases of chronic myelogenous leukemia , MEIS 1 is weakly expressed or not at all . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| The genes encoding Hoxa 9 and Meis 1 are transcriptionally coactivated in a subset of acute myeloid leukemia ( AML ) in mice . ^^^ Although Hoxa 9 and Meis 1 can bind DNA as heterodimers , both can also heterodimerize with Pbx proteins . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Upregulation of Meis 1 and HoxA 9 in acute lymphocytic leukemias with the t ( 4 : 11 ) abnormality . ^^^ A preliminary DNA microarray screen indicated that the Meis 1 , HoxA 9 and AC 133 genes were overexpressed in ALLs with t ( 4 : 11 ) , compared to ALLs with very similar phenotype but without the chromosomal abnormality . ^^^ Meis 1 and HoxA 9 were found expressed in 13 / 14 of ALLs with the t ( 4 : 11 ) and in 8 / 8 of AMLs with ALL 1 rearrangements . ^^^ Coexpression of Meis 1 and HoxA 9 , overexpression of HoxA 10 , and overexpression or fusion of HoxA 9 were previously implicated in certain acute myeloid leukemias in mice and humans . ^^^ The present work suggests that upregulation of Meis 1 , HoxA 9 , and possibly HoxA 10 might also play a role in pathogenesis of acute lymphocytic and acute myeloid leukemias associated with ALL 1 fusions . . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Despite their cooperativity in leukemogenesis , we demonstrated previously that retroviral expression of Hoxa 9 alone in the absence of coexpressed retroviral Meis 1 or of expression of endogenous Meis genes blocks neutrophil and macrophage differentiation of primary myeloid progenitors cultured in granulocyte macrophage colony stimulating factor ( GM CSF ) . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Nup 98 HoxA 9 immortalizes myeloid progenitors , enforces expression of Hoxa 9 , Hoxa 7 and Meis 1 , and alters cytokine specific responses in a manner similar to that induced by retroviral co expression of Hoxa 9 and Meis 1 . ^^^ The association between acute myeloid leukaemia ( AML ) and the aberrant expression of Hoxa 9 is evidenced by ( 1 ) proviral activation of Hoxa 9 and Meis 1 in BXH 2 murine AML , ( 2 ) formation of the chimeric Nup 98 HoxA9 transactivator protein as a consequence of the t ( 7 ; 11 ) translocation in human AML , and ( 3 ) the strong expression of HoxA 9 and Meis 1 in human AML . ^^^ In mouse models , enforced retroviral expression of Hoxa 9 alone in marrow is not sufficient to cause rapid AML , while co expression of Meis 1 and Hoxa 9 induces rapid AML . ^^^ Ectopic expression of Meis 1 in these Hoxa 9 cells suppressed their G CSF induced differentiation , permitted proliferation in SCF , and therein offered a potential explanation of cooperative function . ^^^ Because Meis 1 binds N terminal Hoxa 9 sequences that are replaced by Nup 98 , we hypothesized that Nup 98 HoxA9 might consolidate the biochemical functions of both Hoxa 9 and Meis 1 on target gene promoters and might evoke their same lymphokine responsive profile in immortalized progenitors . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Frequent co expression of HoxA 9 and Meis 1 genes in infant acute lymphoblastic leukaemia with MLL rearrangement . ^^^ We studied the expression of HoxA 9 and Meis 1 by reverse transcriptase polymerase chain reaction analysis in leukaemic cells from cases of infant acute lymphoblastic leukaemia ( ALL , n = 27 ) and childhood ALL ( n = 29 ) . ^^^ These findings indicate that the HoxA 9 and Meis 1 genes are closely associated with MLL gene rearrangement in the development of infant ALL , which represents a distinct entity of childhood ALL . . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Overall , MLL T ALL cases consistently demonstrated increased levels of expression of a subset of major HOX genes HOXA 9 , HOXA 10 , and HOXC 6 and the MEIS 1 HOX coregulator ( P < . 008 , one sided Wilcoxon test ) , a pattern of gene expression that was reiterated in MLL B ALLs . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Hoxa 9 and Meis 1 are key targets for MLL ENL mediated cellular immortalization . ^^^ Microarray analysis performed on these conditionally transformed cells revealed Hoxa 9 and Hoxa 7 as well as the Hox coregulators Meis 1 and Pbx 3 among the targets upregulated by MLL ENL ERtm . ^^^ Moreover , the enforced expression of Hoxa 9 in combination with Meis 1 was sufficient to substitute for MLL ENL ERtm function and to maintain a state of continuous proliferation and differentiation arrest . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Meis 1 and Hoxa 9 expression is upregulated by retroviral integration in murine myeloid leukemias and in human leukemias carrying MLL translocations . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| In primary cells from acute leukemia patients , expression of the genes MEIS 1 , HOXA 5 , HOXA 7 and HOXA 9 has been reported to be correlated with the occurrence of MLL translocations . ^^^ These results suggest that MLL aberrations may regulate MEIS 1 and HOXA 9 gene expression in ALL derived cell lines , while AML derived cell lines express these genes independently of the MLL status . . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Meis 1 mediated apoptosis is caspase dependent and can be suppressed by coexpression of HoxA 9 in murine and human cell lines . ^^^ Coexpression of the homeodomain protein Meis 1 and either HoxA 7 or HoxA 9 is characteristic of many acute myelogenous leukemias . ^^^ Although overexpressing HoxA 9 alone transforms murine bone marrow cells , concurrent Meis 1 overexpression greatly accelerates oncogenesis . ^^^ Coexpressing HoxA 9 with Meis 1 suppresses this apoptosis and provides protection from several apoptosis inducers . ^^^ Pbx 1 , another Meis 1 cofactor , also induces apoptosis ; however , coexpressing HoxA 9 is incapable of rescuing Pbx mediated apoptosis . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| The putative promoter region of GC GARP was found to contain transcription factor binding sites for GATA 1 , IRF 4 , Oct 1 , IRF 7 , IRF 1 , AP 1 , GATA box and NFAT , and the promoter region of GC LRG for MYC MAX , MEIS 1 , ISRE , IK 3 , HOXA 9 and C / EBP alpha . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| We find HoxA 9 mediated CYBB transcription requires Pbx 1 but is inhibited by Meis 1 . ^^^ |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Meis 1 is a homeodomain transcription factor coexpressed with Hoxa 9 in most human acute myeloid leukemias ( AMLs ) . ^^^ In mouse models of leukemia produced by Hoxa 9 , Meis 1 accelerates leukemogenesis . ^^^ Because Hoxa 9 immortalizes myeloid progenitors in the absence of Meis 1 expression , the contribution of Meis 1 toward leukemia remains unclear . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Co expression of HoxA 9 and Meis 1 genes in the KP L RY cell line indicated possible functional similarity between MLL AF 4 and MLL AF5q31 . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| The Hoxa 9 and Meis 1 genes represent important oncogenic collaborators activated in a significant proportion of human leukemias with genetic alterations in the MLL gene . ^^^ Meis 1 and Pbx 1 interaction domain swapping mutants are dysfunctional separately , but restore the full oncogenic activity of Meis 1 when cotransduced in primary cells engineered to overexpress Hoxa 9 , thus implying a modular nature for PIM in Meis 1 accelerated transformation . ^^^ In contrast to Meis 1 , the fusion VP 16 Meis1 is spontaneously oncogenic , and all leukemias harbor genetic activation of endogenous Hoxa 9 and / or Hoxa 7 , suggesting that Hoxa gene activation represents a key event required for the oncogenic activity of VP 16 Meis1 . . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Homeobox transcription factors Meis 1 and Hoxa 9 promote hematopoietic progenitor self renewal and cooperate to cause acute myeloid leukemia ( AML ) . ^^^ While Hoxa 9 alone blocks the differentiation of nonleukemogenic myeloid cell committed progenitors , coexpression with Meis 1 is required for the production of AML initiating progenitors , which also transcribe a group of hematopoietic stem cell genes , including Cd 34 and Flt 3 ( defined as Meis 1 related leukemic signature genes ) . ^^^ Surprisingly , Vp 16 Meis1 ( but not engrailed Meis 1 ) functioned as an autonomous oncoprotein that mimicked combined activities of Meis 1 plus Hoxa 9 , immortalizing early progenitors , inducing low level expression of Meis 1 related signature genes , and causing leukemia without coexpression of exogenous or endogenous Hox genes . ^^^ Strikingly , expression of Hoxa 9 or Hoxa 7 stimulated both leukemic aggressiveness and transcription of Meis 1 related signature genes in Vp 16 Meis1 progenitors . ^^^ Interestingly , while the Hoxa 9 N terminal domain ( NTD ) is essential for cooperative transformation with wild type Meis 1 , it was dispensable in Vp 16 Meis1 progenitors . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Interestingly , MYST 3 CREBBP AML exhibited a characteristic pattern of HOX expression , with up regulation of HOXA 9 , HOXA 10 , and cofactor MEIS 1 and marked down regulation of other homeobox genes . ^^^ This profile , with overexpression of FLT 3 , HOXA 9 , MEIS 1 , AKR7A2 , CHD 3 , and APBA 2 , partially resembles that of AML with MLL rearrangement . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Suppression of MLL AF 4 is paralleled by a decreased expression of the homeotic genes HOXA 7 , HOXA 9 , and MEIS 1 . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| Consistent with signaling downstream of menin , ectopic expression of both Hoxa 9 and Meis 1 rescues colony formation defects in Men 1 excised bone marrow . ^^^ |
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| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P31269 and O00470 |
Pubmed |
SVM Score :0.0 |
| NA |
|