2007
DOI: 10.1158/0008-5472.can-07-2837
|View full text |Cite
|
Sign up to set email alerts
|

Deregulated Overexpression of hCdt1 and hCdc6 Promotes Malignant Behavior

Abstract: The accurate execution of DNA replication requires a strict control of the replication licensing factors hCdt1 and hCdc6. The role of these key replication molecules in carcinogenesis has not been clarified. To examine how early during cancer development deregulation of these factors occurs, we investigated their status in epithelial lesions covering progressive stages of hyperplasia, dysplasia, and full malignancy, mostly from the same patients.

Help me understand this report
View preprint versions

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

13
229
0
46

Year Published

2011
2011
2021
2021

Publication Types

Select...
7

Relationship

0
7

Authors

Journals

citations
Cited by 206 publications
(289 citation statements)
references
References 49 publications
(67 reference statements)
13
229
0
46
Order By: Relevance
“…However, deregulation of the licensing system may also be a primary driver of oncogenesis, at least in some tumour types. For example, over-expression of Cdc6 or Cdt1 have been shown to be oncogenic, and deregulated Mcm7 expression has been linked to tumour formation, progression and malignant transformation in animal models [84][85][86][87][88][89][90]. Oncogenic mutations in genes upstream of the licensing machinery (eg RAS, CYCLINE and CYCLIND1 ) can also impact on tumourigenesis by causing deregulation of the licensing machinery.…”
Section: Dna Replication Licensing and Cancermentioning
confidence: 99%
“…However, deregulation of the licensing system may also be a primary driver of oncogenesis, at least in some tumour types. For example, over-expression of Cdc6 or Cdt1 have been shown to be oncogenic, and deregulated Mcm7 expression has been linked to tumour formation, progression and malignant transformation in animal models [84][85][86][87][88][89][90]. Oncogenic mutations in genes upstream of the licensing machinery (eg RAS, CYCLINE and CYCLIND1 ) can also impact on tumourigenesis by causing deregulation of the licensing machinery.…”
Section: Dna Replication Licensing and Cancermentioning
confidence: 99%
“…The deletion was localized in a Cdt1 region, which is rich in acidic, serine, threonine and proline residues, and corresponds to a previously uncharacterized PEST-like domain (hereafter referred as to 'PEST') that we also detected in other Cdt1 homologues ( Supplementary Fig. S1) 10,24,25 . As the mutation induced an in-frame deletion The homozygous mutation of Cdt1 consists in an 18-nucleotide deletion leading to a six-amino acid in-frame deletion within the PEST domain (D 6 PEST).…”
Section: Resultsmentioning
confidence: 87%
“…Historically, PEST domains are acknowledged to be involved in protein degradation 10,24,25 . Although we cannot formally exclude that the Cdt1 PEST domain might control Cdt1 proteolysis in a short and specific period of the cell cycle, this study shows that Cdt1 degradation is mainly not regulated by its PEST domain.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Moreover, sustained Cdc6 expression has been observed in early stages of tumor development in humans. 1,2 However, no mouse models have been described that directly address the role of Cdc6 in mammalian carcinogenesis in vivo.…”
mentioning
confidence: 99%