S-phase lengthening induced by p16<sup>INK4a</sup>overexpression in malignant cells with wild-type pRb and p53

Chien, Wu Chien; Domenech, Carine; Catallo, Régine; Salles, Gilles; Ffrench, Martine

doi:10.4161/cc.9.16.12600

Cited by 14 publications

(15 citation statements)

References 42 publications

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“…The exogenous p16 INK4a protein was functional since we observed, as previously described (Chien et al, 2010), (i) the binding of p16…”

Section: Ink4amentioning

confidence: 70%

“…INK4a overexpression also induces lengthening of S-phase (Chien et al, 2010). Several reports showed reduced expression of G1-downstream cell cycle regulatory proteins, such as CDK2 and CDK1, acting in S and G2/M phases, respectively, in response to p16…”

Section: Overexpression Of P16mentioning

confidence: 99%

“…INK4a overexpression (Alevizopoulos et al, 1997;Calbo et al, 2004;Chien et al, 2010), but the mechanisms of this inhibition have not been explored until now. In the present study, using the human breast carcinoma MCF7 and the human glioblastoma U87 cell lines as models, we report that p16…”

Section: Overexpression Of P16mentioning

confidence: 99%

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Cyclin-dependent kinase 1 expression is inhibited by p16INK4a at the post-transcriptional level through the microRNA pathway

Domenech

Catallo

et al. 2010

Oncogene

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The p16INK4a protein regulates cell cycle progression mainly by inhibiting the activity of G1-phase cyclin-dependent kinases (CDKs) 4 and 6, the subsequent retinoblastoma protein (pRb) phosphorylation and E2F transcription factor release. The p16INK4a protein can also repress the activity of other transcription factors, such as c-myc, nuclear factorkappaB and c-Jun/AP1. Here, we report that, in two p16WT and p53 WT cell lines (MCF7 and U87), p16INK4a overexpression induces a dramatic decrease in CDK1 protein expression. In response to p16 INK4a, the decreased rate of CDK1 protein synthesis, its unchanged protein half-life, unreduced CDK1 mRNA steady-state levels and mRNA half-life allow us to hypothesize that p16INK4a could regulate CDK1 expression at the post-transcriptional level. This CDK1 downregulation is mediated by the 3 0 -untranslated region (3 0 UTR) of CDK1 mRNA as shown by translational inhibition in luciferase assays and is associated with a modified expression balance of microRNAs (miRNAs) that potentially regulate CDK1, analyzed by TaqMan Human microRNA Array. The p16 INK4a-induced expression of two miRNAs (miR-410 and miR-650 chosen as an example) in MCF7 cells is confirmed by individual reverse transcriptionqPCR. Furthermore, we show the interaction of miR-410 or miR-650 with CDK1-3 0 UTR by luciferase assays. Endogenous CDK1 expression decreases upon both miRNA overexpression and increases with their simultaneous inhibition. The induction of miR-410, but not miR-650 could be related to the pRb/E2F pathway. These results demonstrate the post-transcriptional inhibition of CDK1 by p16 INK4a . We suggest that p16INK4a may regulate gene expression by modifying the functional equilibrium of transcription factors and consequently the expression balance of miRNAs.

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“…The exogenous p16 INK4a protein was functional since we observed, as previously described (Chien et al, 2010), (i) the binding of p16…”

Section: Ink4amentioning

confidence: 70%

Section: Overexpression Of P16mentioning

confidence: 99%

See 1 more Smart Citation

Cyclin-dependent kinase 1 expression is inhibited by p16INK4a at the post-transcriptional level through the microRNA pathway

Domenech

Catallo

et al. 2010

Oncogene

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show abstract

“…Compensatory mechanisms involving other cell cycle regulators bringing about alteration of the cell cycle dynamics [42], and/or eventual activity of Ind on other check points of cell cycle, cannot be ruled out. On the other hand, it has recently been reported that p16 INK4a over-expression can alter cell cycle distribution of malignant cells, with a S-phase lengthening, even in the presence of a hypo-phosphorylated RB [43].…”

Section: Ind Influences Cell Cycle Progressionmentioning

confidence: 99%

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (Caco-2) cells

Naselli

Tesoriere

Caradonna

et al. 2014

Biochemical and Biophysical Research Communications

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“…15,16 In keeping with this concept, elevated expression of p16 ink4a is a potent mechanism for inhibiting proliferation, and is dominant to a variety of mitogenic and oncogenic signals. [17][18][19] Thus, p16 ink4a is a particularly potent effector of cell cycle progression that functions in concert with CDK4/Cyclin D and RB in coordinating proliferation.…”

Section: The Meaning Of P16 Ink4a Expression In Tumorsmentioning

confidence: 99%

The meaning of p16^ink4aexpression in tumors

Witkiewicz¹,

Knudsen²,

Dicker³

et al. 2011

Cell Cycle

238

115

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S-phase lengthening induced by p16^INK4aoverexpression in malignant cells with wild-type pRb and p53

Cited by 14 publications

References 42 publications

Cyclin-dependent kinase 1 expression is inhibited by p16INK4a at the post-transcriptional level through the microRNA pathway

Cyclin-dependent kinase 1 expression is inhibited by p16INK4a at the post-transcriptional level through the microRNA pathway

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (Caco-2) cells

The meaning of p16^ink4aexpression in tumors

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S-phase lengthening induced by p16INK4aoverexpression in malignant cells with wild-type pRb and p53

Cited by 14 publications

References 42 publications

Cyclin-dependent kinase 1 expression is inhibited by p16INK4a at the post-transcriptional level through the microRNA pathway

Cyclin-dependent kinase 1 expression is inhibited by p16INK4a at the post-transcriptional level through the microRNA pathway

Anti-proliferative and pro-apoptotic activity of whole extract and isolated indicaxanthin from Opuntia ficus-indica associated with re-activation of the onco-suppressor p16INK4a gene in human colorectal carcinoma (Caco-2) cells

The meaning of p16ink4aexpression in tumors

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S-phase lengthening induced by p16^INK4aoverexpression in malignant cells with wild-type pRb and p53

The meaning of p16^ink4aexpression in tumors