Last update 01 Nov 2024

CARMIL1

Last update 01 Nov 2024

Basic Info

Synonyms

capping protein regulator and myosin 1 linker 1, Capping protein regulator and myosin 1 linker protein 1, Capping protein, Arp2/3 and myosin-I linker homolog 1

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Introduction

Cell membrane-cytoskeleton-associated protein that plays a role in the regulation of actin polymerization at the barbed end of actin filaments. Prevents F-actin heterodimeric capping protein (CP) activity at the leading edges of migrating cells, and hence generates uncapped barbed ends and enhances actin polymerization, however, seems unable to nucleate filaments (PubMed:16054028). Plays a role in lamellipodial protrusion formations and cell migration (PubMed:19846667).

Drugs associated with CARMIL1

ZINC-65534584

Target

CARMIL1

Mechanism

CARMIL1 inhibitors

Active Org.

Xiamen University

Originator Org.

Xiamen University

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

SKI-73

Target

CARMIL1

Mechanism

CARMIL1 inhibitors

Active Org.

Xiamen University

Originator Org.

Xiamen University

Active Indication

Breast Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CARMIL1

100 Translational Medicine associated with CARMIL1

0 Patents (Medical) associated with CARMIL1

Literatures (Medical) associated with CARMIL1

01 Aug 2024·Journal of Affective Disorders

Ganoderic acid A ameliorates depressive-like behaviors in CSDS mice: Insights from proteomic profiling and molecular mechanisms

Article

Author: Wang, Tian-Yi ; Yin, Zi-Jia ; Xu, Ji-Yi ; Li, Lei ; Ge, Zi-Yu ; Xu, Jin-Jie ; Wang, Gang ; Du, Jing ; Zhang, Yi ; Kan, Wei-Jing ; Feng, Yuan

OBJECTIVEGanoderic Acid A (GAA), a primary bioactive component in Ganoderma, has demonstrated ameliorative effects on depressive-like behaviors in a Chronic Social Defeat Stress (CSDS) mouse model. This study aims to elucidate the underlying molecular mechanisms through proteomic analysis.METHODSC57BL/6 J mice were allocated into control (CON), chronic social defeat stress (CSDS), GAA, and imipramine (IMI) groups. Post-depression induction via CSDS, the GAA and IMI groups received respective treatments of GAA (2.5 mg/kg) and imipramine (10 mg/kg) for five days. Behavioral assessments utilized standardized tests. Proteins from the prefrontal cortex were analyzed using LC-MS, with further examination via bioinformatics and PRM for differential expression. Western blot analysis confirmed protein expression levels.RESULTSChronic social defeat stress (CSDS) induced depressive-like behaviors in mice, which were significantly alleviated by GAA treatment, comparably to imipramine (IMI). Proteomic analysis identified distinct proteins in control (305), GAA-treated (949), and IMI-treated (289) groups. Enrichment in mitochondrial and synaptic proteins was evident from GO and PPI analyses. PRM analysis revealed significant expression changes in proteins crucial for mitochondrial and synaptic functions (namely, Naa30, Bnip1, Tubgcp4, Atxn3, Carmil1, Nup37, Apoh, Mrpl42, Tprkb, Acbd5, Dcx, Erbb4, Ppp1r2, Fam3c, Rnf112, and Cep41). Western blot validation in the prefrontal cortex showed increased levels of Mrpl42, Dcx, Fam3c, Ppp1r2, Rnf112, and Naa30 following GAA treatment.CONCLUSIONGAA exhibits potential antidepressant properties, with its action potentially tied to the modulation of synaptic functions and mitochondrial activities.

01 Jun 2024·International Immunopharmacology

CARMIL1 regulates liver cancer cell proliferation by activating the ERK/mTOR pathway through the TRIM27/p53 axis

Article

Author: Zuo, Shi ; Li, Bo ; Gu, Hua Jian ; Xiao, Benli ; Yang, Sibo ; He, Kun Feng ; Ge, Yuzhen ; Zhao, Rui

Capping protein regulatory factor and myosin 1 linker 1 is termed CARMIL1. CARMIL1 is involved in several physiological processes; it forms an actin filament network and plasma membrane-bound cellular projection tissues and positively regulates the cellular components and tissues. CARMIL1 exhibits important biological functions in cancer; nonetheless, these functions have not been completely explored. We aimed to investigate the novel functions of CARMIL1 in liver cancer, particularly in cell proliferation. The cell counting kit-8, 5-ethynyl-2'-deoxyuridine, Component A experiments, and subcutaneous tumor formation model suggest that CARMIL1 is central to the proliferation of liver cancer cells both in vivo and in vitro. We extracted CARMIL1 samples from The Cancer Genome Atlas Program and analyzed its enrichment. CARMIL1 regulated the pathway activity by affecting the expression of star molecular proteins of the extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR). Moreover, it influenced the proliferation ability of liver cancer cells. Western blotting suggested that CARMIL1 downregulation could affect ERK and mTOR phosphorylation. Results of the co-immunoprecipitation demonstrated that CARMIL1 binds to tripartite motif (TRIM)27, which in turn binds to p53. Subsequently, CARMIL1 can regulate p53 stability and promote its degradation through TRIM27. Additionally, CARMIL1 inhibition enhanced the sensitivity of liver cancer cells to sorafenib. Tumor growth was significantly inhibited in the group treated with sorafenib and CARMIL1, compared with the group treated with CARMIL1 alone. Sorafenib is a first-line targeted chemotherapeutic drug for hepatocellular carcinoma treatment. It increases the long-term survival of hepatocellular carcinoma by 44%. In this study, downregulated CARMIL1 combined with sorafenib significantly reduced the tumor volume and weight of the mouse subcutaneous tumor model, indicating the potential possibility of combining CARMIL1 with sorafenib in hepatocellular carcinoma treatment. In summary, CARMIL1 promotes liver cancer cell proliferation by regulating the TRIM27/p53 axis and activating the ERK/mTOR pathway.

01 Jan 2024·Proteins: Structure, Function, and Bioinformatics

Elastic network model reveals distinct flexibilities of capping proteins bound to CARMIL and twinfilin‐tail

Article

Author: Ota, Motonori ; Koike, Ryotaro

AbstractCapping protein (CP) binds to the barbed end of an actin‐filament and inhibits its elongation. CARMIL binds CP and dissociates it from the barbed end of the actin‐filament. The binding of CARMIL peptide alters the flexibility of CP, which is considered to facilitate the dissociation. Twinfilin also binds to CP through its C‐terminal tail. The complex structures of the CP/twinfilin‐tail (TW‐tail) peptide indicate that the binding sites of CARMIL and TW‐tail overlap. However, TW‐tail binding does not facilitate the dissociation of CP from the barbed end. We extensively investigated the flexibilities of CP in the CP/TW‐tail or CP/CARMIL complexes using an elastic network model and concluded that TW‐tail binding does not alter the flexibility of CP. Our extensive analysis also highlighted that the strong contacts of peptides with the two domains of CP, that is, the CP‐L and CP‐S domains, are key to changing the flexibilities of CP. CARMIL peptides can interact strongly with both of the domains, while TW‐tail peptides exclusively interact with the CP‐S domain because the binding site of TW‐tail on CP relatively shifts to the CP‐S domain compared with that of CP/CARMIL. This result supports our hypothesis that the dissociation of CP from the barbed end is regulated by the flexibility of CP.

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CARMIL1

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