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Last update 08 May 2025

CKAP4

Last update 08 May 2025

Basic Info

Synonyms

63-kDa cytoskeleton-linking membrane protein, CKAP4, CLIMP-63

+ [4]

Introduction

Mediates the anchoring of the endoplasmic reticulum to microtubules. High-affinity epithelial cell surface receptor for the FZD8-related low molecular weight sialoglycopeptide APF/antiproliferative factor. Mediates the APF antiproliferative signaling within cells.

Drugs associated with CKAP4

SND 106

Target

CKAP4

Mechanism

CKAP4 inhibitors

Active Org.

Symeres BV

[+5]

Originator Org.

Pelago Bioscience AB [+5]

Active Indication

Endometrial Carcinoma [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SND 108

Target

CKAP4

Mechanism

CKAP4 inhibitors

Active Org.

Oncolines B.V.

[+5]

Originator Org.

Pelago Bioscience AB [+5]

Active Indication

Endometrial Carcinoma [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CKAP4 targeted aptamer(Wuhan University-)

Target

CKAP4

Mechanism

CKAP4 inhibitors

Active Org.

Wuhan University

Originator Org.

Wuhan University

Active Indication

Neoplasm Metastasis

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CKAP4

100 Translational Medicine associated with CKAP4

0 Patents (Medical) associated with CKAP4

173

Literatures (Medical) associated with CKAP4

01 May 2025·International Journal of Biological Macromolecules

FAM134B-mediated ER-phagy alleviates alcohol-related liver fibrosis by reducing endoplasmic reticulum stress

Article

Author: Lv, Xiongwen ; Gong, Mingxu ; Xia, Guoqing ; Li, Xue ; Wang, Tiantian

BACKGROUNDAlcohol-related liver fibrosis (ALF), a severe stage of alcohol-related liver disease (ALD), currently lacks effective treatments. Endoplasmic reticulum (ER) stress is a key pathological feature of ALF. FAM134B (JK-1, RETREG1), an ER-phagy receptor, mediates ER-phagy to alleviate ER stress and restore ER homeostasis. However, the molecular mechanisms linking ER stress to ALF remain unclear.AIMSThis study aimed to investigate the role and molecular mechanisms of FAM134B in ALF, specifically whether FAM134B-mediated ER-phagy reduces ER stress to mitigate ALF.METHODSWe developed a FAM134B overexpression mouse model using tail vein injection of AAV-8-TBG-m-FAM134B and monitored disease progression in ALF mice. Fibrosis markers (α-SMA, COL1A1), ER stress indicators (GRP78, CHOP, IRE1-α, ATF6), and ER-phagy markers (LC3, p62, VAPB, CANX, Climp63, REEP5) were analyzed. Additionally, further in vitro experiments were carried out to explore whether FAM134B-mediated ER-phagy attenuates ALF by alleviating hepatocyte ER stress.RESULTSFAM134B overexpression increased ER-phagy, reduced ER stress, and ameliorated liver fibrosis. In vitro, FAM134B overexpression promoted autophagy, decreased cytokine secretion, and inhibited hepatic stellate cell (JS-1) and macrophage activation (RAW264.7).CONCLUSIONThese findings suggest that FAM134B-mediated ER-phagy mitigates ALF by alleviating ER stress, providing new targets and intervention strategies for ALF.

24 Apr 2025·Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology

[Inhibition of osteogenic differentiation of mouse bone marrow mesenchymal stem cells and maxillary expansion osteogenesis by Cytoskeleton-associated prorein 4 knockout].

Article

Author: Zhao, Y M ; Chang, S P ; Wang, H Z ; Tao, D H ; He, X N ; Li, B

Objective: To investigate the effect of cytoskeleton-associated protein 4 (CKAP4) gene knockout on maxillary expansion osteogenesis and its regulatory mechanism on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSC). Methods: Sixteen wild type (WT) and sixteen CKAP4 gene knockout (Ckap4^-/-) mice aged 6-8 weeks were selected to establish a mouse model of rapid maxillary expansion. Samples were taken on the 7th and 14th day after the operation. Micro-CT and HE staining were used to evaluate bone regeneration. Tissue proteins in the modeled area were collected, and Western blotting analysis (WB) was used to detect the protein expression levels of alkaline phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN). BMSC were isolated from WT and Ckap4^-/- mice. The expression of surface markers CD29, Sca-1, CD44, CD45, CD34, and CD11b was detected by flow cytometry, and cell proliferation ability was detected by EdU. After 7 days of osteogenic induction, real-time fluorescence quantitative PCR (RT-qPCR) and WB were used to detect the expression levels of RUXN2, ALP, OCN, protein kinase B (AKT), and phosphorylated protein kinase B (p-AKT). After 21 days, alizarin red staining and cetyl pyridine chloride quantification were used to detect the differences in mineralized nodule formation in each group. In CKAP4 gene knockout BMSC, the small-molecule AKT agonist sc79 (4 μg/ml) was added as the intervention group (Ckap4^-/- +sc79), and dimethyl sulfoxide (DMSO) treatment was used as the control group (Ckap4^-/- +DMSO). After osteogenic induction, RT-qPCR, WB, and alizarin red staining were used to compare the osteogenic differentiation differences between the two groups of cells. Results: The micro-CT results showed that at 7 days and 14 days after surgery, the new bone volume in the Ckap4^-/- group [(0.070±0.010) and (0.146±0.019) mm³] was significantly lower than that in the WT group [(0.094±0.006) and (0.196±0.013) mm³] (both P<0.01). HE-stained histological sections showed that the area of new bone tissue in the Ckap4^-/- group at 7 days and 14 days after surgery [(0.101±0.008) and (0.158±0.010) mm²] was also significantly lower than that in the WT group [(0.116±0.005) and (0.183±0.008) mm²] (both P<0.05). WB was used to detect the tissue proteins in the maxillary modeling area of mice in the two groups 7 days after surgery. The results showed that the expression levels of ALP, RUNX2 and OCN in the Ckap4^-/- group were significantly lower than those in the WT group. BMSC from wild-type mice and CKAP4 knockout mice were both positively expressed for CD29, CD44, and Sca-1, and basically not expressed for CD45, CD34, and CD11b. EdU assay showed that there was no significant difference in the proliferation ability of cells in the two groups. After 21 days of osteogenic induction of BMSC, alizarin red staining results showed that the number of mineralized nodules in the Ckap4^-/- group was significantly less than that in the WT group. After adding sc79, the number of mineralized nodules increased significantly, which was consistent with the results of cetyl pyridine chloride quantification. After 7 days of osteogenic induction, of ALP, RUNX2, and OCN It was found that the expression levels in the CKAP4^-/-group (0.751±0.066, 0.484±0.040, 0.679±0.063) were significantly lower than those in the WT group (1.000±0.113, 1.000±0.081, 1.000±0.113) (all P<0.001). The results of WB were consistent with those of RT-qPCR. At the same time, the WB results showed that the level of p-AKT protein in the CKAP4^-/-group (0.518±0.114) was significantly lower than that in the WT group (1.000±0.234) (P<0.05). After treatment with sc79 for 7 days of osteogenic induction, RT-qPCR was used to detect the gene expression levels of ALP, RUNX2, and OCN. The results showed that the expression levels in the CKAP4^-/-+sc79 group (2.755±0.353, 4.800±0.990, 2.524±0.137) were significantly higher than those in the CKAP4^-/-+DMSO group (1.000±0.078, 1.000±0.247, 1.000±0.175) (all P<0.001). Conclusions: CKAP4 knockout inhibits the osteogenic differentiation of BMSC by reducing the activity of the PI3K/AKT signaling pathway, thereby suppressing osteogenesis in maxillary expansion.

03 Apr 2025·Autophagy

CKAP4 in hepatocellular carcinoma: competitive RETREG1/FAM134B binding, reticulophagy regulation, and cancer progression

Article

Author: Chen, Xiaoping ; Tao, Ran ; Xu, Lei ; Zhu, Haidan ; Ge, Qianyun ; Liang, Huifang ; Zhang, Bixiang ; Mo, Jie ; Li, Pengcheng ; Yang, Zhenhua ; Liu, Qiumeng ; Yuan, Chaoyi ; Luo, Yan ; Ning, Deng ; Su, Chen ; Chen, Jin

RETREG1/FAM134B is known for its role as a reticulophagy receptor. Our previous study established that RETREG1 is upregulated in hepatocellular carcinoma (HCC) and contributes to disease progression by activating the AKT signaling pathway. However, the specific mechanisms underlying the elevated expression of RETREG1 in HCC remain unclear. This study unveils the interaction of RETREG1 with CKAP4 and TRIM21. We demonstrated that TRIM21 ubiquitinates RETREG1 at K247 and K252, facilitating its proteasomal degradation. Conversely, CKAP4 shields RETREG1 from degradation by competitively binding to it, revealing a novel post-translational modification mechanism for RETREG1. By modulating RETREG1 expression, CKAP4, and TRIM21 intricately regulate reticulophagy. Additionally, we observed that stress-induced TRIM21 upregulation mitigates the function of RETREG1 to restore ER stress equilibrium. The oncogenic potential of CKAP4 in HCC was demonstrated using various animal models. Clinical sample analyses suggested that CKAP4 is a potential biomarker for HCC prognosis and diagnosis.Abbreviation: AKT: thymoma viral proto-oncogene; aa: amino acid; bp: base pair; CHX: cycloheximide; co-IP: co-Immunoprecipitation; CQ: chloroquine; CKAP4: cytoskeleton-associated protein 4; DKK1: dickkopf WNT signaling pathway inhibitor 1; DUBs: deubiquitinating enzymes; EBSS: Earle's balanced salt solution; EGFP: enhanced green fluorescent protein; ER: endoplasmic reticulum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HCC: hepatocellular carcinoma; HFD: high-fat diet; HiTV: hyperdynamic tail vein injection; IF: immunofluorescence; IHC: immunohistochemistry; IP-MS: immunoprecipitation-mass spectrometry; LIR: LC3-interacting region; mAbs: monoclonal antibodies; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mCherry: monomeric cherry; oe: overexpression; PDX: patient-derived tumor xenograft; reticulophagy: endoplasmic reticulum selective autophagy; RETREG1: reticulophagy regulator 1; RHD: reticulon-homology domain; Tg: thapsigargin; Tm: tunicamycin; TRIM21: tripartite motif-containing 21; UB: ubiquitin; WT: wild-type.

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CKAP4

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