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Last update 08 May 2025

KIF4A

Last update 08 May 2025

Basic Info

Synonyms

Chromokinesin-A, Chromosome-associated kinesin KIF4A, FLJ12530

+ [9]

Introduction

Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis (PubMed:29848660). Translocates PRC1 to the plus ends of interdigitating spindle microtubules during the metaphase to anaphase transition, an essential step for the formation of an organized central spindle midzone and midbody and for successful cytokinesis (PubMed:15297875, PubMed:15625105). May play a role in mitotic chromosomal positioning and bipolar spindle stabilization (By similarity).

Drugs associated with KIF4A

WZ-3146

Target

EGFR T790M x KIF4A

Mechanism

EGFR T790M inhibitors [+1]

Active Org.

Linyi People’s Hospital [+3]

Originator Org.

Dana-Farber Cancer Institute, Inc.

Active Indication

Non-Small Cell Lung Cancer [+2]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KIF4A

100 Translational Medicine associated with KIF4A

0 Patents (Medical) associated with KIF4A

298

Literatures (Medical) associated with KIF4A

09 Apr 2025·mBio

Classical swine fever virus recruits ALIX and ESCRT-III to facilitate viral budding

Article

Author: Chen, Jinxia ; Zhao, Bingqian ; Cheng, Yan ; Wan, Mingyue ; Yang, Hanfei ; Chen, Jing ; Bai, Jishan ; Gao, Fei ; Li, Yuhang ; Zhou, Bin

ABSTRACTClassical swine fever virus (CSFV) incurs substantial economic losses in the global swine industry due to its persistent emergence and re-emergence across various countries. However, the precise mechanisms governing CSFV budding remain inadequately understood. Our study elucidates that the endosomal sorting complex required for transport (ESCRT)-associated protein ALIX, in conjunction with ESCRT-III, plays a pivotal role in orchestrating CSFV budding. Genomic sequence analysis identified a critical interaction between the YPXnL late domain on the E2 protein and ALIX. Through immunoprecipitation and structural domain deletion assays, we demonstrated that the ALIX Bro1 domain specifically recognized viral particles by binding to the YPXnL motif. Immunoelectron and transmission electron microscopy further confirmed that, upon infection, ALIX accumulated at the periphery of subcellular organelles, including COPII vesicles, endosomes, and the Golgi apparatus, thereby facilitating CSFV budding. Our findings also revealed that ESCRT-III subunits CHMP2B, CHMP4B, CHMP7, and VPS4A interacted with ALIX to expedite CSFV budding. Notably, Rab8 activated by Kif4A contributed to the release of CSFV particles by interacting with ALIX and directing ALIX-containing vesicles along microtubules toward the cytosol. Our study demonstrates that ALIX specifically recognizes E2 and orchestrates the recruitment of ESCRT-III and Rab8 to facilitate the vesicular budding of CSFV particles from the Golgi apparatus to the cytosol. Ultimately, virus-laden vesicles propelled by Kif4A are transported along microtubules to the plasma membrane for release. Our findings offer the first comprehensive elucidation of the CSFV budding process and contribute to the identification of antiviral targets, thereby advancing the development of antiviral therapeutics.IMPORTANCEThe endosomal sorting complex required for transport (ESCRT) machinery plays a pivotal role in the sorting of membrane proteins in eukaryotic cells and regulating various stages of infection for numerous viruses. Previous studies have underscored the indispensable role of ESCRT in the cellular entry and replication of classical swine fever virus (CSFV). However, the precise mechanisms by which ESCRT recognizes CSFV particles and initiates viral vesicle budding have remained elusive. This study reveals that the Bro1 domain of ALIX initiates viral budding proximal to the Golgi apparatus by specifically recognizing the YPXnL late domain on the CSFV E2 protein. Mechanistically, ALIX and ESCRT-III facilitate Rab8-regulated endosomal transport of CSFV particles from the Golgi apparatus to the plasma membrane. Subsequently, virions are propelled by the kinesin Kif4A along microtubules for egress into the extracellular space. In summary, these findings significantly advance our understanding of CSFV pathogenesis and offer valuable insights into the vesicular transport and budding mechanisms of CSFV particles.

01 Feb 2025·Combinatorial Chemistry & High Throughput Screening

A Novel KIF4A-related Model for Predicting Immunotherapy Response and Prognosis in Kidney Renal Clear Cell Carcinoma

Article

Author: Yang, Guang Hua ; Liu, Ran Lu ; Wang, Chao ; Ma, Xu Dong ; Wei, Xi Feng

Background:The efficacy of chemotherapy in treating Kidney Renal Clear Cell Carcinoma (KIRC) is limited, whereas immunotherapy has shown some promising clinical outcomes. In this context, KIF4A is considered a potential therapeutic target for various cancers. Therefore, identifying the mechanism of KIF4A that can predict the prognosis and immunotherapy response of KIRC would be of significant importance.Methods:Based on the TCGA Pan-Cancer dataset, the prognostic significance of the KIF4A expression across 33 cancer types was analyzed by univariate Cox algorithm. Furthermore, overlapping differentially expressed genes (DEGs1) between the KIF4A high- and lowexpression groups and DEGs2 between the KIRC and normal groups were also analyzed. Machine learning and Cox regression algorithms were performed to obtain biomarkers and construct a prognostic model. Finally, the role of KIF4A in KIRC was analyzed using quantitative real-time PCR, transwell assay, and EdU experiment.Results:Our analysis revealed that KIF4A was significant for the prognosis of 13 cancer types. The highest correlation with KIF4A was found for KICH among the tumour mutation burden (TMB) indicators. Subsequently, a prognostic model developed with UBE2C, OTX1, PPP2R2C, and RFLNA was obtained and verified with the Renal Cell Cancer-EU/FR dataset. There was a positive correlation between risk score and immunotherapy. Furthermore, the experiment results indicated that KIF4A expression was considerably increased in the KIRC group. Besides, the proliferation, migration, and invasion abilities of KIRC tumor cells were significantly weakened after KIF4A was knocked out.Conclusion:We identified four KIF4A-related biomarkers that hold potential for prognostic assessment in KIRC. Specifically, early implementation of immunotherapy targeting these biomarkers may yield improved outcomes for patients with KIRC.

01 Feb 2025·Experimental Eye Research

Oxygen-dependent alternative mRNA splicing and a cone-specific motor protein revealed by single-cell RNA sequencing in hypoxic retinas

Article

Author: Samardzija, Marijana ; Grimm, Christian ; Nötzli, Sarah ; Ebner, Lynn J A ; Wögenstein, Gabriele M ; Karademir, Duygu

Restricted oxygen supply in the aging eye may lead to hypoxic conditions in the outer retina and contribute not only to physiological aging but also to nonhereditary degenerative retinal diseases. To understand the hypoxic response of specific retinal cell types, we performed single-cell RNA sequencing of retinas isolated from mice exposed to hypoxia. Significantly upregulated expression of marker genes in hypoxic clusters confirmed a general transcriptional response to hypoxia. By focusing on the hypoxic response in photoreceptors, we identified and confirmed a kinesin motor protein (Kif4) that was specifically and strongly induced in hypoxic cones. In contrast, RNA-binding proteins Rbm3 and Cirbp were differentially expressed across clusters but demonstrated isoform switching in hypoxia. The resulting short variants of these gene transcripts are connected to epitranscriptomic regulation, a notion supported by the differential expression of writers, readers and erasers of m⁶A RNA methylations in the hypoxic retina. Our data indicate that retinal cells adapt to hypoxic conditions by adjusting their transcriptome at various levels including gene expression, alternative splicing and the epitranscriptome. Adaptational processes may be cell-type specific as exemplified by the cone-specific upregulation of Kif4 or general like alternative splicing of RNA binding proteins.

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