BTB-ZF Protein Znf131 Regulates Cell Growth of Developing and Mature T Cells

Iguchi, Tomohiro; Aoki, Kazunori; Ikawa, Tomokatsu; Taoka, Masato; Taya, Choji; Yoshitani, Hiroshi; Toma-Hirano, Makiko; Koiwai, Osamu; Isobe, Toshiaki; Kawamoto, Hiroshi; Masai, Hisao; Miyatake, Shoichiro

doi:10.4049/jimmunol.1500602

Cited by 8 publications

(7 citation statements)

References 60 publications

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“…Miz1 is necessary for early T cell development by functioning downstream of IL7 receptor signaling [67, 117]. Finally, Zbtb35 KO mice show severe impairment in the transition from CD4/8 double-negative to double-positive stages [118]. …”

Section: Zbtb Function In Hematopoietic Developmentmentioning

confidence: 99%

Regulation of hematopoietic development by ZBTB transcription factors

Maeda

2016

Int J Hematol

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Hematopoietic development is governed by the coordinated expression of lineage- and differentiation stage-specific genes. Transcription factors play major roles in this process and their perturbation may underlie hematologic and immunologic disorders. Nearly 1900 transcription factors are encoded in the human genome: of these, 49 BTB (for broad-complex, tram-track and bric à brac)-zinc finger transcription factors referred to as ZBTB or POK proteins have been identified. ZBTB proteins, including BCL6, PLZF, ThPOK and LRF, exhibit a broad spectrum of functions in normal and malignant hematopoiesis. This review summarizes developmental and molecular functions of ZBTB proteins relevant to hematology.

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Section: Zbtb Function In Hematopoietic Developmentmentioning

confidence: 99%

Regulation of hematopoietic development by ZBTB transcription factors

Maeda

2016

Int J Hematol

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“…Ablation of ZNF131 in the DN2/DN3 thymocytes (Lck-Cre) does not affect γ δ + T cell development, but significantly reduces the numbers of DN3, DN4 & DP cells, especially the latter two populations ( 72 ). Although the rearrangement of TCR-β locus is intact in ZNF131-deficient DN3 cells, ZNF131 represses the expression of CDKN1A (cyclin dependent kinase inhibitor 1A, also known as P21 Cip1 ) by directly binding to its promoter region, and therefore promotes the (pre-)TCR-induced proliferation of thymic DN3/4 & peripheral mature T cells ( Figures 1A , 2A, B ).…”

Section: Zbtb Proteins Regulating Both the Development And Function Of T Cellsmentioning

confidence: 99%

“…In addition, depletion of ZNF131 at the DP stage (CD4-Cre) has no impact on the survival & differentiation of DP toward CD4 or CD8 SP cells in the thymus. Thus, ZNF131 is mainly involved in the DN-to-DP transition of thymocytes and the homeostasis/proliferation of mature T cells via suppressing CDKN1A ( 72 ). Recently, the same group showed that ZNF131 promotes the early B cell development via similar mechanisms ( 73 ).…”

Section: Zbtb Proteins Regulating Both the Development And Function Of T Cellsmentioning

confidence: 99%

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

Cheng

Gao

et al. 2021

Front. Immunol.

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The development and differentiation of T cells represents a long and highly coordinated, yet flexible at some points, pathway, along which the sequential and dynamic expressions of different transcriptional factors play prominent roles at multiple steps. The large ZBTB family comprises a diverse group of transcriptional factors, and many of them have emerged as critical factors that regulate the lineage commitment, differentiation and effector function of hematopoietic-derived cells as well as a variety of other developmental events. Within the T-cell lineage, several ZBTB proteins, including ZBTB1, ZBTB17, ZBTB7B (THPOK) and BCL6 (ZBTB27), mainly regulate the development and/or differentiation of conventional CD4/CD8 αβ+ T cells, whereas ZBTB16 (PLZF) is essential for the development and function of innate-like unconventional γδ+ T & invariant NKT cells. Given the critical role of T cells in host defenses against infections/tumors and in the pathogenesis of many inflammatory disorders, we herein summarize the roles of fourteen ZBTB family members in the development, differentiation and effector function of both conventional and unconventional T cells as well as the underlying molecular mechanisms.

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“…38 It has also been shown that p21 expression is suppressed in T cells by the zinc finger protein Znf131, thus controlling proliferation of T cells. 39 To further ascertain that p53 is induced by the cMycp14ARF pathway, we inhibited cMyc using 10058-F4, 25 a small-molecule inhibitor that interferes with cMyc/Max heterodimerization, blocking cMyc-mediated transactivation. 40 10058-F4 suppressed cMyc protein expression in activated T cells and also inhibited T cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

cMyc-p53 feedback mechanism regulates the dynamics of T lymphocytes in the immune response

et al. 2016

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Activation and proliferation of T cells are tightly regulated during the immune response. We show here that kinetics of proliferation of PHA activated T cells follows the expression of cMyc. Expression of p53 is also elevated and remains high several days after activation. To investigate the role of p53 in activated T cells, its expression was further elevated with nultin-3 treatment, a small molecule that dissociates the E3 ubiquitin protein ligase MDM2 from p53. Concomitantly, cMyc expression and proliferation decreased. At the other end of the cMyc-p53 axis, inhibition of cMyc with 10058-F4 led to down regulation of p53, likely through the lower level of cMyc induced p14ARF, which is also known to dissociate the p53-MDM2 complex. Both compounds induced cell cycle arrest and apoptosis. We conclude that the feedback regulation between cMyc and p53 is important for the T cell homeostasis. We also show that the two compounds modulating p53 and cMyc levels inhibited proliferation without abolishing the cytotoxic function, thus demonstrating the dichotomy between proliferation and cytotoxicity in activated T cells.

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BTB-ZF Protein Znf131 Regulates Cell Growth of Developing and Mature T Cells

Cited by 8 publications

References 60 publications

Regulation of hematopoietic development by ZBTB transcription factors

Regulation of hematopoietic development by ZBTB transcription factors

ZBTB Transcription Factors: Key Regulators of the Development, Differentiation and Effector Function of T Cells

cMyc-p53 feedback mechanism regulates the dynamics of T lymphocytes in the immune response

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