Transcription factor Zbtb1 interacts with bridging factor Lmo2 and maintains the T-lineage differentiation capacity of lymphoid progenitor cells

Koizumi, Maria; Kama, Yuichi; Hirano, Kazuyuki; Endo, Yusuke; Tanaka, Tomoaki; Hozumi, Katsuto; Hosokawa, Hiroyuki

doi:10.1016/j.jbc.2022.102506

Cited by 2 publications

(3 citation statements)

References 63 publications

(85 reference statements)

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“…LMO2 could regulate the expression of oncogenes and cell differentiation of AML cell lines through complex formation with MYB [ 34 ]. The interaction between LMO2 and transcription factor Zbtb1 is necessary to maintain the T-lineage differentiation capacity of lymphoid progenitor cells [ 35 ]. Mass spectrometric analysis showed that LDB1 ranked first among the proteins interacting with LMO2 in AML cells.…”

Section: Discussionmentioning

confidence: 99%

LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1

Lu,

Wang,

Fang

et al. 2023

Cell Death Dis

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One of the characteristics of leukemia is that it contains multiple rearrangements of signal transduction genes and overexpression of non-mutant genes, such as transcription factors. As an important regulator of hematopoietic stem cell development and erythropoiesis, LMO2 is considered an effective carcinogenic driver in T cell lines and a marker of poor prognosis in patients with AML with normal karyotype. LDB1 is a key factor in the transformation of thymocytes into T-ALL induced by LMO2, and enhances the stability of carcinogenic related proteins in leukemia. However, the function and mechanism of LMO2 and LDB1 in AML remains unclear. Herein, the LMO2 gene was knocked down to observe its effects on proliferation, survival, and colony formation of NB4, Kasumi-1 and K562 cell lines. Using mass spectrometry and IP experiments, our results showed the presence of LMO2/LDB1 protein complex in AML cell lines, which is consistent with previous studies. Furthermore, in vitro and in vivo experiments revealed that LDB1 is essential for the proliferation and survival of AML cell lines. Analysis of RNA-seq and ChIP-Seq results showed that LDB1 could regulate apoptosis-related genes, including LMO2. In LDB1-deficient AML cell lines, the overexpression of LMO2 partially compensates for the proliferation inhibition. In summary, our findings revealed that LDB1 played an important role in AML as an oncogene, and emphasize the potential importance of the LMO2/LDB1 complex in clinical treatment of patients with AML.

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Section: Discussionmentioning

confidence: 99%

LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1

Lu,

Wang,

Fang

et al. 2023

Cell Death Dis

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“…During early T cell development, Lyl1 is important to make ETP to DN2a progression possible and to turn on Gfi1 ( 200 ), which encodes a zinc finger repressor protein that is crucial for survival of early lymphoid progenitors in the presence of Notch signals ( 172 ). Recent studies also show a supportive role of Lmo2 in maintaining the T-lineage competence of immortalized progenitor-like cells ( 81 , 195 ). Thus, although silenced in mature T cells, Lmo2 and Lyl1 contribute to the T-lineage developmental competence of hematopoietic progenitors.…”

Section: Gene Regulatory Network Models For Early T Cell Development ...mentioning

confidence: 93%

“…These form a complex with E protein (e.g. E2A or HEB), a GATA family factor, and an Ldb1 “bridge”, in which the Lyl1/E protein heterodimer interacts with DNA and the association of Lmo2 with Lyl1 stabilizes the complex ( 155 , 156 , 195 , 196 ). In hematopoietic stem and progenitor cells, the complex often involves the related bHLH factor SCL instead of Lyl1 ( 197 , 198 ).…”

Section: Gene Regulatory Network Models For Early T Cell Development ...mentioning

confidence: 99%

Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells

Shin

Rothenberg

2023

Front. Immunol.

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T cells develop from multipotent progenitors by a gradual process dependent on intrathymic Notch signaling and coupled with extensive proliferation. The stages leading them to T-cell lineage commitment are well characterized by single-cell and bulk RNA analyses of sorted populations and by direct measurements of precursor-product relationships. This process depends not only on Notch signaling but also on multiple transcription factors, some associated with stemness and multipotency, some with alternative lineages, and others associated with T-cell fate. These factors interact in opposing or semi-independent T cell gene regulatory network (GRN) subcircuits that are increasingly well defined. A newly comprehensive picture of this network has emerged. Importantly, because key factors in the GRN can bind to markedly different genomic sites at one stage than they do at other stages, the genes they significantly regulate are also stage-specific. Global transcriptome analyses of perturbations have revealed an underlying modular structure to the T-cell commitment GRN, separating decisions to lose “stem-ness” from decisions to block alternative fates. Finally, the updated network sheds light on the intimate relationship between the T-cell program, which depends on the thymus, and the innate lymphoid cell (ILC) program, which does not.

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Transcription factor Zbtb1 interacts with bridging factor Lmo2 and maintains the T-lineage differentiation capacity of lymphoid progenitor cells

Cited by 2 publications

References 63 publications

LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1

LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1

Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells

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