A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells

Yeh, Elizabeth S.; Cunningham, Melissa A.; Arnold, Hugh; Chasse, Dawn; Monteith, Teresa; Ivaldi, Giovanni Battista; Hahn, William C.; Stukenberg, P. Todd; Shenolikar, Shirish; Uchida, Takafumi; Counter, Christopher M.; Nevins, Joseph R.; Means, Anthony R.; Sears, Rosalie C.

doi:10.1038/ncb1110

Cited by 693 publications

(792 citation statements)

References 32 publications

Supporting

Mentioning

736

Contrasting

Unclassified

Order By: Relevance

“…58 Other substrates such as c-Myc are instead isomerized to a trans-conformation and their stability decreases as a result of Pin1 activity. 60 Accumulating evidence indicates that, upon phosphorylation, Pin1 regulates the timing of p53 activation by rendering p53 suitable for subsequent modifications and modulating its interaction with DNA and cofactors (Figure 4). Barely detectable under normal growth conditions, the interaction between p53 and Pin1 markedly increases after genotoxic stress, on expression of activated oncogenes, and probably in response to a wide range of other stimuli (see above references).…”

Section: The Prolyl Isomerase Pin1mentioning

confidence: 99%

Some p53-binding proteins that can function as arbiters of life and death

2006

View full text Add to dashboard Cite

Four sets of p53-binding proteins are discussed in this review. These are the E2F family, the ASPP family, Y-boxbinding protein YB1, and the prolyl isomerase Pin1. Each appears to play a role in the decision by p53 to induce an arrest of cell proliferation or apoptosis and they may also be independent markers of cancer. Their activities appear to be linked with the cell cycle and they may also interact with each other. In this review, the properties of each protein class are discussed as well as how they affect p53 functions. A model is proposed as to how their activities might be coordinated.

show abstract

Section: The Prolyl Isomerase Pin1mentioning

confidence: 99%

Some p53-binding proteins that can function as arbiters of life and death

2006

View full text Add to dashboard Cite

show abstract

“…MAPK and AKT) and protoncogenes (e.g. Myc) (Sontag, 2001;Yuan et al, 2002;Yeh et al, 2004). Furthermore, the PP2A subunit A per se also has been described to be genetically or functionally altered in different types of cancer.…”

Section: Protein Phosphatase 2a (Pp2a) a Phosphatase With Tumour Supmentioning

confidence: 99%

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

Perrotti

Neviani

2006

Br J Cancer

View full text Add to dashboard Cite

The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and contributes to disease progression. Imatinib mesylate, a BCR/ABL kinase inhibitor, is effective in most of chronic phase CML patients. However, a significant percentage of CML patients develop resistance to imatinib and/or still progresses to blast crisis, a disease stage that is often refractory to imatinib therapy. Furthermore, there is compelling evidence indicating that the CML leukaemia stem cell is also resistant to imatinib. Thus, there is still a need for new drugs that, if combined with imatinib, will decrease the rate of relapse, fully overcome imatinib resistance and prevent blastic transformation of CML. We recently reported that the activity of the tumour suppressor protein phosphatase 2A (PP2A) is markedly inhibited in blast crisis CML patient cells and that molecular or pharmacologic re-activation of PP2A phosphatase led to growth suppression, enhanced apoptosis, impaired clonogenic potential and decreased in vivo leukaemogenesis of imatinib-sensitive and -resistant (T315I included) CML-BC patient cells and/or BCR/ABL þ myeloid progenitor cell lines. Thus, the combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients.

show abstract

“…Isomerization of proline (Pro) residues by this protein has been shown to promote dephosphorylation of various molecules by PP2A (Zhou et al, 2000;Yeh et al, 2004;Monje et al, 2005). Pin1 binds Ser/Thr-Pro motifs through its WW motif and binds to a diverse set of substrates, including Cdc25 and Tau (Zhou et al, 2000;Stukenberg and Kirschner, 2001).…”

Section: Introductionmentioning

confidence: 99%

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

Arnold

Lilly

et al. 2007

Oncogene

View full text Add to dashboard Cite

The Pim protein kinases are serine threonine protein kinases that regulate important cellular signaling pathway molecules, and enhance the ability of c-Myc to induce lymphomas. We demonstrate that a cascade of events controls the cellular levels of Pim. We find that overexpression of the protein phosphatase (PP) 2A catalytic subunit decreases the activity and protein levels of Pim-1. This effect is reversed by the application of okadaic acid, an inhibitor of PP2A, and is blocked by SV40 small T antigen that is known to disrupt B subunit binding to PP2A A and C subunits. Pim-1 can coimmunoprecipitate with the PP2A regulatory B subunit, B56b, but not B56a, c, d, e or B55a. Using short hairpin RNA targeted at B56b, we demonstrate that decreasing the level of B56b increases the half-life of Pim-1 from 0.7 to 2.8 h, and decreases the ubiquitinylation level of Pim-1. We also find that Pin1, a prolyl-isomerase, is capable of binding Pim-1 and leads to a decrease in the protein level of Pim-1. On the basis of these observations, we hypothesize that phosphorylated Pim-1 binds Pin1 allowing the interaction of PP2A through B56b. Dephosphorylation of Pim-1 then allows for ubiquitinylation and protein degradation of Pim-1.

show abstract

A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells

Cited by 693 publications

References 32 publications

Some p53-binding proteins that can function as arbiters of life and death

Some p53-binding proteins that can function as arbiters of life and death

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

Contact Info

Product

Resources

About