STAT5b: A master regulator of key biological pathways

Smith, M.; Satter, Lisa R. Forbes; Vargas-Hernández, Alexander

doi:10.3389/fimmu.2022.1025373

Cited by 25 publications

(11 citation statements)

References 150 publications

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“…19 STAT5b activation is involved in the expression of genes that participate in cell development, proliferation, and survival. 20 It regulates cell proliferation and induces leukemia through JAK-STAT signaling pathways. 9 STAT5b plays a role in preventing further differentiation of hematopoietic cells together with the corepressor complex of deacetylase, this complex cannot be released by ATRA.…”

Section: Discussionmentioning

confidence: 99%

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Identification of concurrent STAT3::RARA and RARA::STAT5b fusions in a variant APL case

Tao,

Cen,

et al. 2023

Molecular Carcinogenesis

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Acute promyelocytic leukemia (APL) with typically PML::RARA fusion gene caused by t (15;17) (q22; q12) was distinguished from other types of acute myeloid leukemia. In a subset of patients with APL, t (15;17) (q22;q21) and PML::RARA fusion cannot be detected. In this report, we identified the coexistence of STAT3::RARA and RARA::STAT5b fusions for the first time in a variant APL patient lacking t (15;17)(q22;q21)/PML::RARA fusion. Then, this patient was resistant to all‐trans retinoic acid combined arsenic trioxide chemotherapy. Accurate detection of RARA gene partners is crucial for variant APL, and effective therapeutic regime is urgently needed.

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Section: Discussionmentioning

confidence: 99%

“…Exons 2–19 of STAT5b encode a slightly smaller peptide of 787 amino acid residues 19 . STAT5b activation is involved in the expression of genes that participate in cell development, proliferation, and survival 20 . It regulates cell proliferation and induces leukemia through JAK‐STAT signaling pathways 9 .…”

Section: Discussionmentioning

confidence: 99%

Identification of concurrent STAT3::RARA and RARA::STAT5b fusions in a variant APL case

Tao,

Cen,

et al. 2023

Molecular Carcinogenesis

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“…IL‐2 receptor signaling is critical for T‐cell function and the development of regulatory T cells and STAT5b is the essential transcription factor for these immune processes. In addition to immune and hematopoietic functions, STAT5b plays a role in the growth hormone receptor pathway, as well as other important cellular growth factors 116 …”

Section: Stat5b‐related Diseasementioning

confidence: 99%

JAK/STAT defects and immune dysregulation, and guiding therapeutic choices

Chaimowitz,

Smith,

Forbes Satter

2024

Immunological Reviews

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SummaryInborn errors of immunity (IEIs) encompass a diverse spectrum of genetic disorders that disrupt the intricate mechanisms of the immune system, leading to a variety of clinical manifestations. Traditionally associated with an increased susceptibility to recurrent infections, IEIs have unveiled a broader clinical landscape, encompassing immune dysregulation disorders characterized by autoimmunity, severe allergy, lymphoproliferation, and even malignancy. This review delves into the intricate interplay between IEIs and the JAK–STAT signaling pathway, a critical regulator of immune homeostasis. Mutations within this pathway can lead to a wide array of clinical presentations, even within the same gene. This heterogeneity poses a significant challenge, necessitating individually tailored therapeutic approaches to effectively manage the diverse manifestations of these disorders. Additionally, JAK–STAT pathway defects can lead to simultaneous susceptibility to both infection and immune dysregulation. JAK inhibitors, with their ability to suppress JAK–STAT signaling, have emerged as powerful tools in controlling immune dysregulation. However, questions remain regarding the optimal selection and dosing regimens for each specific condition. Hematopoietic stem cell transplantation (HSCT) holds promise as a curative therapy for many JAK–STAT pathway disorders, but this procedure carries significant risks. The use of JAK inhibitors as a bridge to HSCT has been proposed as a potential strategy to mitigate these risks.

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“…Signal transducer and activator of transcription (STAT) is a unique family of proteins that can bind to DNA 316 . The STAT family consists of STAT1, STAT2, STAT3, STAT4, STAT5, and STAT6 317,318 . STAT proteins, particularly STAT3 and 5 transduce signals from cytokines and growth factors through their receptors to the nucleus to regulate expression of a variety of genes, leading to cell proliferation, apoptosis inhibition, and chemo‐resistance 319,320 (PMID: 36596870).…”

Section: Crbn Ligands and Their Utilizations In Protacsmentioning

confidence: 99%

PROTACs: A novel strategy for cancer drug discovery and development

Han

Sun

2023

MedComm

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Proteolysis targeting chimera (PROTAC) technology has become a powerful strategy in drug discovery, especially for undruggable targets/proteins. A typical PROTAC degrader consists of three components: a small molecule that binds to a target protein, an E3 ligase ligand (consisting of an E3 ligase and its small molecule recruiter), and a chemical linker that hooks first two components together. In the past 20 years, we have witnessed advancement of multiple PRO-TAC degraders into the clinical trials for anticancer therapies. However, one of the major challenges of PROTAC technology is that only very limited number of E3 ligase recruiters are currently available as E3 ligand for targeted protein degradation (TPD), although human genome encodes more than 600 E3 ligases. Thus, there is an urgent need to identify additional effective E3 ligase recruiters for TPD applications. In this review, we summarized the existing RING-type E3 ubiquitin ligase and their small molecule recruiters that act as effective E3 ligands of PRO-TAC degraders and their application in anticancer drug discovery. We believe that this review could serve as a reference in future development of efficient E3 ligands of PROTAC technology for cancer drug discovery and development.

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STAT5b: A master regulator of key biological pathways

Cited by 25 publications

References 150 publications

Identification of concurrent STAT3::RARA and RARA::STAT5b fusions in a variant APL case

Identification of concurrent STAT3::RARA and RARA::STAT5b fusions in a variant APL case

JAK/STAT defects and immune dysregulation, and guiding therapeutic choices

PROTACs: A novel strategy for cancer drug discovery and development

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