The importance of CDC27 in cancer: molecular pathology and clinical aspects

Kazemi-Sefat, Golnaz Ensieh; Keramatipour, Mohammad; Talebi, Saeed; Kavousi, Kaveh; Sajed, Roya; Kazemi-Sefat, Nazanin Atieh; Mousavizadeh, Kazem

doi:10.1186/s12935-021-01860-9

Cited by 32 publications

(23 citation statements)

References 75 publications

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“…The major functional isomers of CDC27 are encoded by 19 exons, and CDC27 has two tetratricopeptide repeat (TPR) domains, five TPR motifs at the N-terminal domain and nine TPR motifs in the C-terminal domain ( 44 ). The protein encoded by CDC27 is a component of APC, which had a TPR sequence of its own that is necessary for interaction with certain proteins ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity

et al. 2022

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BackgroundAs genetic genetic factors are important in SLE, so screening causative genes is of great significance for the prediction and early prevention in people who may develop SLE. At present, it is very difficult to screen causative genes through pedigrees. The analytical method described herein can be used to screen causative genes for SLE and other complex diseases through pedigrees.MethodsFor the first time, 24 lupus pedigrees were analyzed by combining whole exon sequencing and a variety of biological information tools including common-specific analysis, pVAAST (pedigree variant annotation, analysis and search tool), Exomiser (Combining phenotype and PPI associated analysis), and FARVAT (family based gene burden), and the causative genes of these families with lupus identified. Selected causative genes in peripheral-blood mononuclear cells (PBMCs) were evaluated by quantitative polymerase chain reaction (qPCR).ResultsCell division cycle 27 (CDC27) was screened out by common-specific analysis and Exomiser causative gene screening. FARVAT analysis on these families detected only CDC27 at the extremely significant level (false discovery rate <0.05) by three family-based burden analyses (BURDEN, CALPHA, and SKATO). QPCR was performed to detect for CDC27 in the PBMCs of the SLE family patients, sporadic lupus patients, and healthy people. Compared with the healthy control group, CDC27 expression was low in lupus patients (familial and sporadic patients) (P<0.05) and correlated with lupus activity indicators: negatively with C-reactive protein (CRP) (P<0.05) and erythrocyte sedimentation rate (P<0.05) and positively with complement C3 and C4 (P<0.05). The CDC27 expression was upregulated in PBMCs from SLE patients with reduced lupus activity after immunotherapy (P<0.05). Based on Receiver operating characteristic (ROC) curve analysis, the sensitivity and specificity of CDC27 in diagnosing SLE were 82.30% and 94.40%.ConclusionThe CDC27 gene, as found through WES combined with multiple analytical method may be a causative gene of lupus. CDC27 may serve as a marker for the diagnosis of SLE and is closely related to the lupus activity. We hope that the analytical method in this study will be used to screen causative genes for other diseases through small pedigrees, especially among non-close relatives.

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Section: Discussionmentioning

confidence: 99%

A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity

et al. 2022

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“…CDC27 is one of the main components of the anaphase-promoting complex/cyclosome and overexpression and variations in CDC27 expression may affect the cell cycle, mitosis, cancer pathogenesis and prognosis [ 60 , 61 ]. Thus far, there is no specific targeted therapy for CDC27 .…”

Section: Discussionmentioning

confidence: 99%

Whole-Exome Sequencing of HPV Positive Tonsillar and Base of Tongue Squamous Cell Carcinomas Reveals a Global Mutational Pattern along with Relapse-Specific Somatic Variants

Ährlund‐Richter

Holzhauser

Dalianis

et al. 2021

Cancers

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To identify predictive/targetable markers in human papillomavirus positive (HPV+) tonsillar and base of tongue cancer (TSCC/BOTSCC), whole-exome sequencing (WES) of tumours of patients with/without recurrence was performed. Forty primary tumours and adjacent normal tissue were separated by micro-dissection from formalin-fixed paraffin-embedded tissue from patients treated with curative intent 2000–2014 at Karolinska University Hospital. Successful sequencing was obtained in primary tumours of 18 patients without and primaries of 17 with local or distant recurrence, as well as in 10 corresponding recurrences (i.e., five local relapses and five distant metastases) from these 17 patients. One variant—a high-impact deletion in the CDC27 gene—was observed only in primaries of 5/17 patients that had a recurrence after full treatment but in none of those without recurrence. In addition, 3 variants and 26 mutated genes, including CDC27, BCLAF1 and AQP7, were present in at least 30% of all primary tumours independent of prognosis. To conclude, a CDC27 deletion was specific and found in ~30% of samples from patients with a local relapse/distant metastasis and could, therefore, potentially be a prospective marker to predict prognosis. Commonly mutated genes, such as BCLAF1, should be further studied in the context of targeted therapy.

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“…Among them, Lee and his colleagues reported that HSF1 interacts with CDC20 [ 110 ]. This interaction inhibits the association between CDC20 and CDC27, which is one of the canonical subunits of the APC/C complex and is important for mitotic exit and transition into G 1 phase [ 111 , 112 , 113 ] and suppresses the phosphorylation and ubiquitination activity of the APC/C complex [ 110 ]. Subsequently, they showed that HSF1 is localized to the centromere in mitosis and especially to the spindle poles in metaphase, and that phosphorylated HSF1 undergoes ubiquitin degradation during spindle pole localization [ 114 ].…”

Section: Degradation Of Hsfs During Cell Cyclementioning

confidence: 99%

Cell Cycle Regulation by Heat Shock Transcription Factors

Tokunaga

Otsuyama

Hayashida

2022

Cells

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Cell division and cell cycle mechanism has been studied for 70 years. This research has revealed that the cell cycle is regulated by many factors, including cyclins and cyclin-dependent kinases (CDKs). Heat shock transcription factors (HSFs) have been noted as critical proteins for cell survival against various stresses; however, recent studies suggest that HSFs also have important roles in cell cycle regulation-independent cell-protective functions. During cell cycle progression, HSF1, and HSF2 bind to condensed chromatin to provide immediate precise gene expression after cell division. This review focuses on the function of these HSFs in cell cycle progression, cell cycle arrest, gene bookmarking, mitosis and meiosis.

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The importance of CDC27 in cancer: molecular pathology and clinical aspects

Cited by 32 publications

References 75 publications

A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity

A Novel Gene CDC27 Causes SLE and Is Associated With the Disease Activity

Whole-Exome Sequencing of HPV Positive Tonsillar and Base of Tongue Squamous Cell Carcinomas Reveals a Global Mutational Pattern along with Relapse-Specific Somatic Variants

Cell Cycle Regulation by Heat Shock Transcription Factors

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