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Last update 08 May 2025

MAP3K11

Last update 08 May 2025

Basic Info

Synonyms

MAP3K11, MEKK11, Mitogen-activated protein kinase kinase kinase 11

+ [5]

Introduction

Activates the JUN N-terminal pathway. Required for serum-stimulated cell proliferation and for mitogen and cytokine activation of MAPK14 (p38), MAPK3 (ERK) and MAPK8 (JNK1) through phosphorylation and activation of MAP2K4/MKK4 and MAP2K7/MKK7. Plays a role in mitogen-stimulated phosphorylation and activation of BRAF, but does not phosphorylate BRAF directly. Influences microtubule organization during the cell cycle.

Drugs associated with MAP3K11

MD300

Target

HPK1 x MAP3K11

Mechanism

HPK1 inhibitors [+1]

Active Org.

MD Biolab Co., Ltd.

Originator Org.

MD Biolab Co., Ltd.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CEP-1347

Target

MAP3K11

Mechanism

MAP3K11 inhibitors

Active Org.

Kyowa Hakko Kogyo Co., Ltd.

Originator Org.

H. Lundbeck A/S

Active Indication

Nervous System Diseases

Inactive Indication

Asthma [+2]

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

OST-246

Target

JAK3 x MAP3K11 x TYK2

Mechanism

JAK3 inhibitors [+2]

Active Org.

Oncostellae SL

Originator Org.

Oncostellae SL

Active Indication

Autoimmune Diseases [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with MAP3K11

EUCTR2004-002812-27-IS

/ Not yet recruitingPhase 2

A prospective, randomised, double-blind, placebo-controlled, parallel group dose ranging study in asthma patients in Iceland to assess the safety, tolerability and efficacy of the MLK inhibitor, CEP-1347

Start Date04 May 2005

Sponsor / Collaborator

deCODE Genetics ehf

NCT00040404

/ TerminatedPhase 2/3

A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study to Assess the Efficacy and Safety of CEP-1347 in Patients With Parkinson's Disease

The purpose of this study is to establish safety for CEP-1347 and to determine an efficacious dose in the treatment of Parkinson's disease.

Start Date01 Mar 2002

Sponsor / Collaborator

Cephalon, Inc.

[+2]

100 Clinical Results associated with MAP3K11

100 Translational Medicine associated with MAP3K11

0 Patents (Medical) associated with MAP3K11

593

Literatures (Medical) associated with MAP3K11

04 Mar 2025·Proceedings of the National Academy of Sciences

Bipartite binding of the intrinsically disordered scaffold protein JIP1 to the kinase JNK1

Article

Author: Tengo, Maud ; Boeri Erba, Elisabetta ; Delaforge, Elise ; Orand, Thibault ; Blackledge, Martin ; Jensen, Malene Ringkjøbing ; Tengo, Laura ; Lee, Alexandra ; Palencia, Andrés ; Kragelj, Jaka ; Davis, Roger J.

Scaffold proteins are key players in many signaling pathways where they ensure spatial and temporal control of molecular interactions by simultaneous tethering of multiple signaling components. The protein JIP1 acts as a scaffold within the c-Jun N-terminal kinase (JNK) signaling pathway by assembling three kinases, MLK3, MKK7, and JNK, into a macromolecular complex that enables their specific activation. The recruitment of these kinases depends on the 450-amino acid intrinsically disordered tail of JIP1, however, the structural details of this tail and the molecular mechanisms by which it binds kinases have remained elusive. Here, we provide an atomic resolution structural description of the JIP1 tail, and we study its interaction with the kinase JNK1. Using NMR spectroscopy, we show that JNK1 not only engages with the well-known docking site motif (D-motif) of JIP1, but also interacts with a noncanonical F-motif. We determine the crystal structure of the JIP1–JNK1 complex at 2.35 Å resolution revealing a bipartite binding mode of JIP1. Our work provides insights into the sequence determinants of F-motifs suggesting that these motifs may be more prevalent in JNK substrates than previously recognized. More broadly, our study highlights the power of NMR spectroscopy in uncovering kinase interaction motifs within disordered scaffold proteins, and it paves the way for atomic-resolution interaction studies of JIP1 with its multitude of interaction partners.

10 Feb 2025·Journal of Cancer

Prognostic Significance of CDK1 in Ovarian and Cervical Cancers

Article

Author: Chen, Huaqiu ; Li, Zhenqi ; Xu, Yonghong ; Chen, Chaowen ; Xu, Cong ; Wang, Guangming

Background: Ovarian cancer (OC) and cervical cancer (CC) are the leading causes of death among women. Therefore, identifying markers for early detection and treatment is critical. CDK1 governs the G2/M transition of the cell cycle and is a significant regulatory protein of the cycle. RO-3306 and UBE2C are related to CDK1 expression and might jointly facilitate the development of OC. CDK1 and CDK2 phosphorylate MLK3, which plays an important role in the invasion and proliferation of OC cells. Furthermore, miR-490-3P targets CDK1 and restrains the growth of ovarian tumors. CDK1 also plays a crucial part in the progression of CC. For instance, CDK1 overexpression can rescue the effect of RCC1 knockdown, which is involved in key processes, such as cytoplasmic transport, on G1 cell cycle progression. Using bioinformatics analysis, we evaluated the functional enrichment and role of the co-expressed gene CDK1 in these two cancers and its impact on their prognoses. Methods: First, we screened public datasets for OC- and CC-associated DEGs and identified intersecting genes. Enrichment analyses of these genes revealed key biological pathways and processes. We then generated protein-protein interaction networks to identify central genes and important gene modules. Results: Additional enrichment analyses revealed that cell cycle regulation and germ cell maturation were the primary processes regulated by these core genes. We also examined the function of CDK1 in OC and CC, demonstrating its overexpression and its association with particular immunological cell infiltration patterns. Furthermore, CDK1 mutational burden, copy number variation, and patient survival analyses indicated that CDK1 may be a useful prognostic marker. Finally, immunohistochemical examination confirmed the expression of some candidate genes in clinical samples. Conclusion: These findings shed light on the molecular causes of OC and CC and will aid the identification of novel targets for future research regarding these cancers, including their diagnosis and treatment.

01 Feb 2025·iScience

Trillin inhibits MAP3K11/NF-κB/COX-2 signaling pathways through upregulation of miR-145-5p in castration-resistant prostate cancer

Article

Author: Zhao, Haolin ; He, Chengjian ; Wang, Yanlong ; Hao, Wenjun ; Liu, Zhiyu ; Liang, Peng ; Wang, Ying ; Gao, Xiang ; Wang, Liang ; Yu, Zhenlong ; Peng, Yulin

Castration-resistant prostate cancer (CRPC) presents a significant challenge in treatment following androgen deprivation therapy. This study evaluates Trillin, a compound with antioxidant and anti-inflammatory properties, for its therapeutic potential against CRPC. Using DU145 and PC3 cell lines and a mouse xenograft model, we demonstrate that Trillin effectively inhibits CRPC cell viability, proliferation, migration, and invasion while promoting apoptosis and cell-cycle arrest. Mechanistic investigations reveal that Trillin disrupts NF-κB/COX-2 signaling by downregulating MAP3K11 and COX-2 and inhibiting the nuclear translocation of NF-κB subunits. Additionally, Trillin enhances the expression of miR-145-5p, further modulating pathways critical for CRPC progression. These findings suggest that Trillin may offer a promising alternative approach for targeting CRPC, highlighting its potential as a therapeutic agent to improve patient outcomes.

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