Last update 19 Sep 2024

STAT5B

Last update 19 Sep 2024

Basic Info

Synonyms

Signal transducer and activator of transcription 5B, STAT5B

Introduction

Carries out a dual function: signal transduction and activation of transcription (PubMed:29844444). Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription. Positively regulates hematopoietic/erythroid differentiation.

Drugs associated with STAT5B

IST5-002

Target

STAT5A x STAT5B

Mechanism

STAT5A inhibitors [+1]

Active Org.

Thomas Jefferson University

Originator Org.

Thomas Jefferson University

Active Indication

Philadelphia chromosome positive chronic myelogenous leukemia [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

AK-2292

Target

STAT5A x STAT5B

Mechanism

STAT5A inhibitors [+1]

Active Org.

University of Michigan

Originator Org.

University of Michigan

Active Indication

Acute Myeloid Leukemia

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with STAT5B

100 Translational Medicine associated with STAT5B

0 Patents (Medical) associated with STAT5B

1,282

Literatures (Medical) associated with STAT5B

31 Dec 2024·OncoImmunology

LFA-1 regulated by IL-2/STAT5 pathway boosts antitumor function of intratumoral CD8 ⁺ T cells for improving anti-PD-1 antibody therapy

Article

Author: Liu, Yaqing ; Shen, Chunyi ; Liu, Fengsen ; Shan, Jiqi ; Han, Dong ; Zhang, Yi ; Li, Congcong ; Jing, Wei ; Ping, Yu

Anti-PD-1 antibody therapy has achieved success in tumor treatment; however, the duration of its clinical benefits are typically short. The functional state of intratumoral CD8⁺ T cells substantially affects the efficacy of anti-PD-1 antibody therapy. Understanding how intratumoral CD8⁺ T cells change will contribute to the improvement in anti-PD-1 antibody therapy. In this study, we found that tumor growth was not arrested after the late administration of anti-PD-1 antibody and that the antitumor function of CD8⁺ T cells decreased with tumor progression. The results of the RNA sequencing of CD8⁺ T cells infiltrating the tumor site on days 7 and 14 showed that the cell adhesion molecule Lymphocyte Function-associated Antigen-1 (LFA-1) participates in regulating the antitumor function of CD8⁺ T cells and that decreased LFA-1 expression in intratumoral CD8⁺ T cells is associated with tumor progression. By analyzing the Gene Expression Omnibus (GEO) database and our results, we found that the antitumor function of intratumoral CD8⁺ T cells with high LFA-1 expression was stronger. The formation of immune synapses is impaired in Itgal-si CD8⁺ T cells, resulting in decreased anti-tumor function. LFA-1 expression in intratumoral CD8⁺ T cells is regulated by the IL-2/STAT5 pathway. The combination of IL-2 and anti-PD-1 antibody effectively enhanced LFA-1 expression and the antitumor function of intratumoral CD8⁺ T cells. The adoptive transfer of OT-1 T cells overexpressing LFA-1, STAT5A, or STAT5B resulted in higher antitumor function, deferred tumor growth, and prolonged survival. These findings indicate that LFA-1-mediated immune synapse acts as a regulator of the antitumor function of intratumoral CD8⁺ T cells, which can be applied to improve anti-PD-1 antibody therapy.

01 Oct 2024·Insect Biochemistry and Molecular Biology

JAK and STAT5B mediate olfactory response of migratory locusts to their own volatiles

Article

Author: Zhang, Lichen ; Ma, Zongyuan ; Liu, Jipeng

Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signaling affect social aggregation, mood and psychiatric disorders, nociceptive and depressive behaviors. Olfactory dysfunction is one of the distinct symptoms of these behaviors, but function and mechanism of JAK and STAT in modulating olfaction remain largely unknown. Migratory locusts show olfactory preference for their own volatiles. We thus use this animal model to explore functions and mechanisms of JAK and STAT5B in mediating olfaction response to their own volatiles. Tissue distribution study shows that JAK and STAT5B express in antennae and brains, especially in antennal lobes and mushroom bodies in locust brains, and knockdown of these two genes by RNA interference (RNAi) in antennae and brains results in the loss of olfactory preference for locust volatiles, including chemical odorants indole and β-ionone. RNA-seq analysis reveals that JAK and STAT5B RNAi knockdown downregulates a functional class of transcripts in nucleoprotein complex, including heterogeneous nuclear ribonucleoprotein C (hnRNPC) and small nuclear ribonucleoprotein polypeptide F (SNRPF). HnRNPC and SNRPF mRNAs and proteins are also expressed in antennae and brains, and RNAi knockdown of these two genes reduces the percentage of locusts preferring volatiles, including chemical odorants indole and β-ionone. Furthermore, RNAi knockdown of dopamine receptor 1 (DopR1) results in the decrease of JAK mRNA level in antennae, and JAK/STAT5B, hnRNPC and SNRPF are required for dopamine receptor 1 (DopR1) to modulate olfactory preference for their own volatiles. This study confirms that JAK/STAT5B signaling modulates olfaction by affecting expression levels of hnRNPC and SNRPF, and this pathway is also required for DopR1 to modulate olfactory preference for their own volatiles. These findings highlight novel roles of JAK and STAT5B in modulating olfactory preference. This study provides novel insights into functional links among JAK/STAT5B signaling, RNA binding proteins and DopR1 underlying the modulation of olfactory behaviors.

01 Sep 2024·Molecular and Cellular Endocrinology

Epigenetic impact of hypothyroidism on the functional differentiation of the mammary gland in rats

Article

Author: Ortiz, Irina ; Carón, Rubén Walter ; Pascual, Lourdes Inés ; Hapon, María Belén ; Gamarra-Luques, Carlos ; Campo Verde Arbocco, Fiorella ; García, Daiana

Mammary gland (MG) lactogenic differentiation involves epigenetic mechanisms. We have previously shown that hypothyroidism (HypoT) alters the MG transcriptome in lactation. However, the role of thyroid hormones (T3 and T4 a. k.a. THs) in epigenetic differentiation of MG is still unknown. We used a model of post-lactating HypoT rats to study in MG: a) Methylation and expression level of Gata3, Elf5, Stat6, Stat5a, Stat5b; b) Expression of Lalba, IL-4Rα and Ncoa1 mRNA; c) Histone H3 acetylation and d) Estrogen and progesterone concentration in serum. HypoT increases the estrogen serum level, decreases the progesterone level, promotes methylation of Stat5a, Stat5b and Stat6, decreasing their mRNA level and of its target genes (Lalba and IL-4Rα) and increases the Ncoa1 mRNA expression and histone H3 acetylation level. Our results proved that HypoT alters the post-lactation MG epigenome and could compromise mammary functional differentiation.

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STAT5B

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