• Biomolecules & Therapeutics
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• 제4권4호
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• pp.398-401
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• 1996

The glucose transporters found in the plasma membrane of all animal cells are known to have 12 putative transmembrane domains. Among 7 cytoplasmic loops, the fourth loop is the largest one. Since previous studies showed that cofilin, an actin-modulating protein, was found to interact with the largest cytoplasmic loop of (Na, K)ATPase, we tested if cofilin interacts with the largest cytoplasmic loop of Glut4. We demonstrated by the two-hybrid system that the largest cytoplasmic loop of Glut4 did not show any interaction with cofilin, suggesting that cofilin is not required for the membrane targeting process of other membrane proteins but only for a P-type ATPase.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9593-9597
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• 2014

Ursolic acid, extracted from the traditional Chinese medicine bearberry, can induce apoptosis of gastric cancer cells. However, its pro-apoptotic mechanism still needs further investigation. More and more evidence demonstrates that mitochondrial translocation of cofilin-1 appears necessary for the regulation of apoptosis. Here, we report that ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis. These findings imply that induction of apoptosis by ursolic acid stems primarily from the activation of ROCK1 and PTEN, resulting in the translocation of cofilin-1 from cytoplasm to mitochondria, release of cytochrome c, activation of caspase-3 and caspase-9, and finally inducing apoptosis of gastric cancer SGC-7901 cells.

• The Korean Journal of Physiology and Pharmacology
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• 제16권3호
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• pp.159-165
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• 2012

Squamous cell carcinoma (SCC) and adenocarcinoma (AC) are the major histological types of non-small cell lung carcinoma (NSCLC). Although both SCCs and ACs have been characterized histologically and clinically, the precise mechanisms underlying their migration and invasion are not yet known. Here, we address the involvement in NSCLC of the p21-associated kinase1 (Pak1)/LIM kinase1 (LIMK1)/cofilin pathway, which recently has been reported to play a critical role in tumor migration and invasion. The Pak1/LIMK1/cofilin pathway was evaluated in tumors from SCC (n=35) and AC (n=35) patients and in SCC- and AC-type cell lines by western blotting, immunohistochemistry, and in vitro migration and invasion assays. The levels of phosphorylated Pak1, LIMK1, and cofilin in lung tumor tissues from SCC patients were increased as compared to normal tissues. In addition, immunohistochemistry showed greater expression of phosphorylated cofilin in SCC tissues. Expression of phosphorylated Pak1 and LIMK1 proteins was also significantly higher in SCC-type cells than in AC-type cells. Moreover, migration and invasion assays revealed that a higher percentage of SCC type cells exhibited migration and invasion compared to AC type cells. Migration was also decreased in LIMK1 knockdown SK-MES-1 cells. These findings suggest that the activation of the Pak1/LIMK1/cofilin pathway could preferentially contribute to greater tumor migration and invasion in SCC, relative to that in AC.

• BMB Reports
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• 제54권12호
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• pp.614-619
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• 2021

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), which is a highly aggressive cancer. HBV X protein (HBx), one of four HBV gene products, plays pivotal roles in the development and metastasis of HCC. It has been reported that HBx induces liver cancer cell migration and reorganizes actin cytoskeleton, however the molecular basis for actin cytoskeleton reorganization remains obscure. In this study, we for the first time report that HBx promotes actin polymerization and liver cancer cell migration by regulating calcium modulated protein, calmodulin (CaM). HBx physically interacts with CaM to control the level of phosphorylated cofilin, an actin depolymerizing factor. Mechanistically, HBx interacts with CaM, liberates Hsp90 from its inhibitory partner CaM, and increases the activity of Hsp90, thus activating LIMK1/cofilin pathway. Interestingly, the interaction between HBx and CaM is calcium-dependent and requires the CaM binding motif on HBx. These results indicate that HBx modulates CaM which plays a regulatory role in Hsp90/LIMK1/cofilin pathway of actin reorganization, suggesting a new mechanism of HBV-induced HCC metastasis specifically derived by HBx.

• BMB Reports
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• 제50권6호
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• pp.335-340
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• 2017

Although doxorubicin (Dox)-induced oxidative stress is known to be associated with cytotoxicity, the precise mechanism remains unclear. Genotoxic stress not only generates free radicals, but also affects actin cytoskeleton stability. We showed that Dox-induced RhoA signaling stimulated actin cytoskeleton alterations, resulting in central stress fiber disruption at early time points and cell periphery cortical actin formation at a later stage, in HeLa cells. Interestingly, activation of a cofilin phosphatase, chronophin (CIN), was initially evoked by Dox-induced RhoA signaling, resulting in a rapid phosphorylated cofilin turnover leading to actin cytoskeleton remodeling. In addition, a novel interaction between CIN and $14-3-3{\zeta}$ was detected in the absence of Dox treatment. We demonstrated that CIN activity is quite contrary to $14-3-3{\zeta}$ binding, and the interaction leads to enhanced phosphorylated cofilin levels. Therefore, initial CIN activation regulation could be critical in Dox-induced actin cytoskeleton remodeling through RhoA/cofilin signaling.

• 한국발생생물학회지:발생과생식
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• 제26권1호
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• pp.23-36
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• 2022

Pharyngeal pouches, a series of outgrowths of the pharyngeal endoderm, are a key epithelial structure governing facial skeleton development in vertebrates. Pouch formation is achieved through collective cell migration and rearrangement of pouch-forming cells controlled by actin cytoskeleton dynamics. While essential transcription factors and signaling molecules have been identified in pouch formation, regulators of actin cytoskeleton dynamics have not been reported yet in any vertebrates. Cofilin1-like (Cfl1l) is a fish-specific member of the Actin-depolymerizing factor (ADF)/Cofilin family, a critical regulator of actin cytoskeleton dynamics in eukaryotic cells. Here, we report the expression and function of cfl1l in pouch development in zebrafish. We first showed that fish cfl1l might be an ortholog of vertebrate adf, based on phylogenetic analysis of vertebrate adf and cfl genes. During pouch formation, cfl1l was expressed sequentially in the developing pouches but not in the posterior cell mass in which future pouch-forming cells are present. However, pouches, as well as facial cartilages whose development is dependent upon pouch formation, were unaffected by loss-of-function mutations in cfl1l. Although it could not be completely ruled out a possibility of a genetic redundancy of Cfl1l with other Cfls, our results suggest that the cfl1l expression in the developing pouches might be dispensable for regulating actin cytoskeleton dynamics in pouch-forming cells.

• Mycobiology
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• 제43권3호
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• pp.272-279
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• 2015

To screen molecular chaperones similar to small heat shock proteins (sHsps), but without ${\alpha}$-crystalline domain, heat-stable proteins from Schizosaccharomyces pombe were analyzed by 2-dimensional electrophoresis and matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Sixteen proteins were identified, and four recombinant proteins, including cofilin, NTF2, pyridoxin biosynthesis protein (Snz1) and Wos2 that has an ${\alpha}$-crystalline domain, were purified. Among these proteins, only Snz1 showed the anti-aggregation activity against thermal denaturation of citrate synthase. However, pre-heating of NTF2 and Wos2 at $70^{\circ}C$ for 30 min, efficiently prevented thermal aggregation of citrate synthase. These results indicate that Snz1 and NTF2 possess molecular chaperone activity similar to sHsps, even though there is no ${\alpha}$-crystalline domain in their sequences.

• 한국임상수의학회지
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• 제28권1호
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• pp.75-80
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• 2011

Proteomics is a useful approach to know protein expression, post-translational modification and protein function. We investigated the protein expression pattern and identity in pigs fed with the tissue culture medium waste after harvest of Korean wild ginseng (TCM-KWG) (Panax ginseng). Two groups (n = 30/group) of pigs were administered with 0 (control) and 16 ml/L (treatment) TCM-KWG through drinking water. After 4 weeks, we examined the protein expression pattern of longissimus dorsi muscle by Two-dimensional electrophoresis analysis. TCM-KWG treatment significantly increased two spot's density, and markedly reduced one spot's density in the muscles. We identified 3 proteins (heat shock protein 90-alpha, myosin binding protein and cofilin 2) by the ESI-MS/MS (Q-TOF2, Micromass). These results demonstrate that TCM-KWG treatment may play a protection role against physiological stress in pigs, like as increased heat shock protein 90-alpha.

• 생명과학회지
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• 제21권10호
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• pp.1401-1406
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• 2011

면역세포는 외부 병원체 감염, 자연적 순환에 대하여 형태변화를 수반한다. T세포는 염증, 면역 감시, 이동, 그리고 혈관통과를 위해 uropod, filopodia, lamellipodia, 및 microvilli를 생산한다. 짧고 손가락 처럼 생긴 microvilli는 순환하고 있는 포유동물 면역세포 표면을 덮고 있다. 단핵세포와 호중구의 세포표면은 많이 다른데 membrane ruffle을 함유하고 있다. 본 연구는, T세포의 microvilli에 대하여 actin cytoskeleton과의 연관성에 대하여 탐구하였다. Actin 파괴자인 cytochalasin D 처리 후 SEM관찰을 통해서, Jurkat T세포의 microvilli를 보면 빠르게 사라지는 것을 알 수 있었다. 이와는 대조적으로 RhoA의 activator인 PMA는 LIMK와 cofilin 신호 전달을 통해서 microvilli 두께가 확장되는 것을 관찰 하였다. 또한, cytochalasin D 처리는 EL4 T세포의 극성을 사라지게 하는 것으로 보아 F-actin은 T세포의 극성 유지에도 영향을 미친다. 이상의 결과는 Actin cytoskeleton은 T세포에서 microvilli와 극성 유지에 관여하고 있는 것을 제시한다.

• 한국어업기술학회:학술대회논문집
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• 한국어업기술학회 2000년도 추계수산관련학회 공동학술대회발표요지집
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• pp.175-176
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• 2000

PtdIns(4)P와 PtdIns(4,5)P$_2$등과 같은 폴리포스이노시타이드(Polyphosph-oinositide)는 여러 가지 호르몬 및 성장인자들에 의한 세포의 신호전달기작에 있어서 중요한 역할을 한다. 이들은 세포내 여러효소 및 단백질의 활성을 조절하기도 하고, cofilin(1), destrin(2), $\alpha$-actinin(3), gCap39(4) 및 CapZ등과 같은 여러 actin binding protein들의 성질을 변화시키기도 한다. (중략)