Identification and characterization of CAC1 as a novel CDK2-associated cullin

Kong, Ying; Kang, Nan; Yin, Yuxin

doi:10.4161/cc.8.21.9955

Cited by 24 publications

(31 citation statements)

References 24 publications

(24 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…It embraces an open reading frame sequence which encodes a 37 kDa protein of 369 amino acids [5]. The CAC1 protein contains a cullin domain between amino acids 137 and 250, and is therefore classified as a member of the cullin family of E3 ubiquitin ligases [5]. Histological investigations had established a possible association of CAC1 expression with pathological features and clinical stages of colorectal carcinoma patients [5].…”

Section: Introductionmentioning

confidence: 99%

“…The CAC1 protein contains a cullin domain between amino acids 137 and 250, and is therefore classified as a member of the cullin family of E3 ubiquitin ligases [5]. Histological investigations had established a possible association of CAC1 expression with pathological features and clinical stages of colorectal carcinoma patients [5]. Moreover, CAC1 , in vitro , was expressed in a cell cycle-dependent manner with high expression in the late G1 to S phase [5].…”

Section: Introductionmentioning

confidence: 99%

“…Histological investigations had established a possible association of CAC1 expression with pathological features and clinical stages of colorectal carcinoma patients [5]. Moreover, CAC1 , in vitro , was expressed in a cell cycle-dependent manner with high expression in the late G1 to S phase [5]. Notably, CAC1 could promote cell cycle progression and stimulate the kinase activity of CDK2 [5].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, CAC1 , in vitro , was expressed in a cell cycle-dependent manner with high expression in the late G1 to S phase [5]. Notably, CAC1 could promote cell cycle progression and stimulate the kinase activity of CDK2 [5]. Nevertheless, little is known about its expression and biological characteristics in gastric cancer.…”

Section: Introductionmentioning

confidence: 99%

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CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line

et al. 2013

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BackgroundGastric cancer is a common and highly lethal malignancy in the world, but its pathogenesis remains elusive. In this study, we focus on the biological functions of CDK-associated Cullin1 (CAC1), a novel gene of the cullin family, in gastric cancer, which may help us to further understand the origin of this malignancy.MethodsThe AGS and MGC803 gastric cancer cell lines and the GES-1 gastric mucosa cell line were selected for study. At first, CAC1 expressions of those cell lines were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blot examinations, then CAC1 small interfering RNA (CAC1-siRNA) were designed and transfected into the AGS cell line with a relatively high level of CAC1. Once CAC1 was silenced, a series of biological characteristics of AGS cells such as cell proliferation, cell cycle, apoptosis, and expressions of apoptosis-related genes (P53, BCL2 and BAX) were determined by MTT, flow cytometry, qRT-PCR and western blot, respectively.ResultsCAC1 expression of AGS or MGC803 was much higher than that of GES-1. After CAC1 expression was effectively depressed by RNA interference in AGS cells, significant cell growth inhibition occurred. Furthermore, the proportion of cells treated with CAC1-siRNA increased in the G1 phase and decreased in the S phase, indicative of G1 cell cycle arrest. More importantly, the proportions of early/late apoptosis in AGS cells were enhanced with cis-diaminedichloroplatinum (cisplatin, CDDP) treatment, but to a higher extent with cisplatin plus CAC1-siRNA. Interestingly, BCL2 mRNA copies showed about a 30% decrease in the cisplatin group, but dropped by around 60% in the cisplatin plus CAC1-siRNA group. Conversely, the P53 mRNA expressions obtained nearly a two-fold increase in the cisplatin group, in addition to a five-fold increase in the cisplatin plus CAC1-siRNA group, and the BAX mRNA levels had almost a two- and four-fold augmentation, respectively. Meanwhile, P53, BAX and BCL2 showed the same alteration patterns in western blot examinations.ConclusionsCAC1 can promote cell proliferation in the AGS gastric cancer cell line. Moreover, it can prevent AGS cells from experiencing cisplatin-induced apoptosis via modulating expressions of P53, BCL2 and BAX.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line

et al. 2013

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Expression of the Newly Identified Gene CAC1 in the Hippocampus of Alzheimer’s Disease Patients

et al. 2012

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Alzheimer's disease (AD), the most common form of senile dementia, is associated with neurodegeneration. The development of Alzheimer's disease is related to abnormalities of cell cycle regulation. Preliminary work showed that a novel gene, CAC1, was highly expressed in tumors and had an oncogene-like function related to cell cycle regulation. The pathogenesis of AD is still incompletely understood. In this study, we measured the expression level of CAC1 in the hippocampus of AD patients to explore the involvement of CAC1 in the development of AD. Our findings showed that the expression level of CAC1 in the hippocampus of AD patients was significantly lower than that of normal controls. The reduction of CAC1 expression did not affect tau/p-tau-396, amyloid precursor protein or apolipoprotein E4 in the in vitro model. A reduction of cyclin E was detected after a CAC1-knockdown. Interestingly, we found that the knockdown of CAC1 by RNAi led to an increase in oxidative stress and the level of p53 protein in SHSY-5Y cells. The expression of CAC1 in SHSY-5Y cells protected the cells from apoptosis induced by Aβ toxicity or oxidative stress. These results established that CAC1 is an important factor for the protection of cells against Aβ toxicity and oxidative stress.

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The role of cullin proteins in gastric cancer

Chen

Yao²

2015

Tumor Biol.

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The cullin proteins are a family of scaffolding proteins that associate with RING proteins and ubiquitin E3 ligases and mediate substrate-receptor bindings. Thus, cullin proteins regulate the specificity of ubiquitin targeting in the regulation of proteins involved in various cellular processes, including proliferation, differentiation, and apoptosis. There are seven cullin proteins that have been identified in eukaryotes: CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, and CUL7/p53-associated parkin-like cytoplasmic protein. All of these proteins contain a conserved cullin homology domain that binds to RING box proteins. Cullin-RING ubiquitin ligase complexes are activated upon post-translational modification by neural precursor cell-expressed, developmentally downregulated protein 8. The aberrant expression of several cullin proteins has been implicated in many cancers though the significance in gastric cancer has been less well investigated. This review provides the first systematic discussion of the associations between all members of the cullin protein family and gastric cancer. Functional and regulatory mechanisms of cullin proteins in gastric carcinoma progression are also summarized along with a discussion concerning future research areas. Accumulating evidence suggests a critical role of cullin proteins in tumorigenesis, and a better understanding of the function of these individual cullin proteins and their targets will help identify potential biomarkers and therapeutic targets.

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Identification and characterization of CAC1 as a novel CDK2-associated cullin

Cited by 24 publications

References 24 publications

CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line

CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line

Expression of the Newly Identified Gene CAC1 in the Hippocampus of Alzheimer’s Disease Patients

The role of cullin proteins in gastric cancer

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