Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding

Liao, Peng; Zeng, Shelya X.; Zhou, Xiang; Chen, Tianjian; Zhou, Fangjian; Cao, Bo; Jung, Ji Hoon; Sal, Giannino Del; Luo, Shuhong; Lu, Hua

doi:10.1016/j.molcel.2017.11.006

Cited by 89 publications

(111 citation statements)

References 63 publications

Supporting

Mentioning

105

Contrasting

Order By: Relevance

“…12 However, It is well known that different CDK play distinct roles in different tumor cell cycles. 13 For the first time, we discovered through a serum starvation experiment that CDK2 was consistent with the trend of SEPT2 from the early G1 phase ( Figure 1A). Subsequently, the expression of CDK2 and SEPT2 in different cell cycles was analyzed using the double thymidine synchronization method.…”

Section: Correlated Dynamic Expression Of Cyclindependent Kinase 2 supporting

confidence: 52%

“…Studies have suggested that NEDD5 (SEPT2) is not only expressed in all brain tumors but also changes with the cell cycle progression, reaching a peak in the G2/M phase . However, It is well known that different CDK play distinct roles in different tumor cell cycles . For the first time, we discovered through a serum starvation experiment that CDK2 was consistent with the trend of SEPT2 from the early G1 phase (Figure A).…”

Section: Resultsmentioning

confidence: 54%

See 1 more Smart Citation

Coupling function of cyclin‐dependent kinase 2 and Septin2 in the promotion of hepatocellular carcinoma

Zhang

et al. 2018

Cancer Science

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is a common and aggressive malignant tumor with a poorly defined molecular mechanism. Cyclin‐dependent kinase 2 (CDK2) and Septin2 (SEPT2) are 2 known oncogenic molecules but the mechanism of functional interactions remains unclear. Here, we interestingly found that CDK2 and SEPT2 show very similar dynamic expression during the cell cycle. Both CDK2 and SEPT2 show the highest protein levels in the G2/M phase, resulting in CDK2 interacting with SEPT2 and stabilizing SEPT2 in HCC. In a panel of 8 pairs of fresh HCC tissues and corresponding adjacent tissues, both western blot and immunohistochemistry (IHC) assays demonstrate that CDK2 expression is highly correlated with SEPT2. HCC with high expression of both CDK2 and SEPT2 are more likely to relapse. This observation is further demonstrated by a large panel of 100 HCC patients. In this large panel, high expression of both CDK2 and SEPT2 significantly correlates with tumor differentiation and microvascular invasion, which is an independent prognostic factor in HCC patients. In summary, our results reveal a cooperative function between CDK2 and SEPT2. HCC with high expression of CDK2 and SEPT2 might be more aggressive and respond poorly to current therapy.

show abstract

Section: Correlated Dynamic Expression Of Cyclindependent Kinase 2 supporting

confidence: 52%

Section: Resultsmentioning

confidence: 54%

Coupling function of cyclin‐dependent kinase 2 and Septin2 in the promotion of hepatocellular carcinoma

Zhang

et al. 2018

Cancer Science

View full text Add to dashboard Cite

show abstract

“…In cancer cells expressing GOF mutant p53, groups of genes that belong to the CBP (39), NRF2 (40), c-MYC (41, 42), ETS1/2 (43, 44), networks as well as those that are involved in chromatin methylation/acetylation (MLL1/2, MOZ; 45) are transactivated (mtp53 reviewed in 38, 44–46). Preferential binding of ETS1 to WTp53 and ETS2 to mtp53 have been reported, suggesting tumor-suppressive function for the former and oncogenic function for the latter, which is discussed in this review.…”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of ETS1 and ETS2 proteins in cancer

Fry

Inoue

2018

Cancer Rep Rev

View full text Add to dashboard Cite

The ETS transcription factors regulate expression of genes involved in normal cell development, proliferation, differentiation, angiogenesis, and apoptosis, consisting of 28 family members in humans. Dysregulation of these transcription factors facilitates cell proliferation in cancers, and several members participate in invasion and metastasis by activating gene transcription. ETS1 and ETS2 are the founding members of the ETS family and regulate transcription by binding to ETS sequences. They are both involved in oncogenesis and tumor suppression depending on the biological situations used. The essential roles of ETS proteins in human telomere maintenance have been suggested, which have been linked to creation of new Ets binding sites. Recently, preferential binding of ETS2 to gain-of-function mutant p53 and ETS1 to wild type p53 (WTp53) has been suggested, raising the tumor promoting role for the former and tumor suppressive role for the latter. The oncogenic and tumor suppressive functions of ETS1 and 2 proteins have been discussed.

show abstract

“…The prolyl isomerase PIN1, a critical modifier of multiple signaling pathways, is overactivated in cancers, and it promotes cancer and cancer stem cells by disrupting the balance of oncogenes and tumor suppressors (28)(29)(30)(31). Inactivation of PIN1 function conversely curbs tumor growth and cancer stem cell expansion, restores chemosensitivity, and blocks metastatic spread, thus providing a rationale for a therapeutic strategy based on PIN1 inhibition (32)(33)(34). However, the available PIN1 inhibitors either lack the required specificity and potency or cannot efficiently enter cells to inhibit PIN1 function in vivo (35).…”

Section: Discussionmentioning

confidence: 99%

Shrimp miRNA suppresses the stemness of human cancer stem cellsviathe PIN1 pathway

Zhang

2019

FASEB j.

View full text Add to dashboard Cite

A tumor can be regarded as a cell mass with a biologic hierarchy that is orchestrated by cancer stem cells. The specific features of cancer stem cells may result from a series of gene expression regulatory mechanisms. As important regulatory factors of gene expression, microRNAs (miRNAs) have critical roles in the self‐renewal, pluripotency, differentiation, and tumorigenicity of cancer stem cells. However, the effects of animal miRNAs on cancer stem cells have not been investigated extensively. Here, we report that miRNA of a shrimp, Marsupenαeus jαponicus (mja‐miR‐35‐3p), which possesses antiviral activity in shrimp, could suppress the proliferation of melanoma and breast cancer stem cells, but not cancer nonstem cells, by arresting the cell cycle in the G1 phase and inducing apoptosis. Shrimp mja‐miR‐35‐3p (named mja‐miR‐35) targets the human peptidylprolyl cis/trans isomerase, never in mitosis gene a‐interacting 1 (PIN1) gene, which is up‐regulated in cancer stem cells. The results indicated that PIN1 silencing caused cell cycle arrest in the G1 phase, induced apoptosis, and decreased the sphere‐forming capacity of cancer stem cells, but not cancer nonstem cells, showing that PIN1 had beneficial effects against the stemness of cancer stem cells. The in vivo data revealed that shrimp mja‐miR‐35 suppressed the stemness of cancer stem cells in mice by inhibiting the PIN1 antiapoptotic–cell cycle pathway. These findings demonstrated that the miRNAs of aquatic animals might be an important source for discovering human antitumor drugs.—Zhang, S., Zhang, X. Shrimp miRNA suppresses the stemness of human cancer stem cells via the PIN1 pathway. FASEB J. 33, 10767–10779 (2019). http://www.fasebj.org

show abstract

Mutant p53 Gains Its Function via c-Myc Activation upon CDK4 Phosphorylation at Serine 249 and Consequent PIN1 Binding

Cited by 89 publications

References 63 publications

Coupling function of cyclin‐dependent kinase 2 and Septin2 in the promotion of hepatocellular carcinoma

Coupling function of cyclin‐dependent kinase 2 and Septin2 in the promotion of hepatocellular carcinoma

Aberrant expression of ETS1 and ETS2 proteins in cancer

Shrimp miRNA suppresses the stemness of human cancer stem cellsviathe PIN1 pathway

Contact Info

Product

Resources

About