p53DINP1, a p53-Inducible Gene, Regulates p53-Dependent Apoptosis

Okamura, Shu; Arakawa, Hirofumi; Tanaka, Toshihiro; Nakanishi, Hiroshi; Ng, Ching Ching; Taya, Yoichi; Monden, Morito; Nakamura, Yusuke

doi:10.1016/s1097-2765(01)00284-2

Cited by 312 publications

(295 citation statements)

References 26 publications

Supporting

Mentioning

277

Contrasting

Unclassified

Order By: Relevance

“…Besides PML, other proteins function as cofactors for HIPK2-mediated p53Ser46 phosphorylation by binding to p53 and HIPK2. These include the PML-nuclear body components Sp100 (Moller et al, 2003b) and the death domain-associated protein Daxx (Li et al, 2007a), the p53-inducible factor p53DINP1/ TP53INP1 (Okamura et al, 2001;Tomasini et al, 2003) and Axin (Rui et al, 2004), a master scaffold for the regulation of the Wnt/b-catenin signaling pathway (Kikuchi, 1999;Peifer and Polakis, 2000) ( Figure 2). Axin (amino acids 678-753) physically interacts with HIPK2 (amino acids 935-1050) as well as p53-activating HIPK2-mediated p53Ser46 phosphorylation and facilitates p53-dependent transcriptional activity and apoptosis (Rui et al, 2004).…”

Section: Hipk2 Phosphorylates P53 At Ser46 and Mediates Apoptosismentioning

confidence: 99%

Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells

et al. 2010

View full text Add to dashboard Cite

The p53 protein is the most studied tumor suppressor and the p53 pathway has been shown to mediate cellular stress responses that are disrupted when cancer develops. After DNA damage, p53 is activated as transcription factor to directly induce the expression of target genes involved in cell-cycle arrest, DNA repair, senescence and, importantly, apoptosis. Post-translational modifications of p53 are essential for the activation of p53 and for selection of target genes. The tumor suppressor homeodomain-interacting protein kinase-2 (HIPK2) is a crucial regulator of p53 apoptotic function by phosphorylating its N-terminal serine 46 (Ser46) and facilitating Lys382 acetylation at the C-terminus. HIPK2 is activated by numerous genotoxic agents and can be deregulated in tumors by several conditions including hypoxia. Recent findings suggest that HIPK2 active/inactive protein can affect p53 function in multiple and unexpected ways. This makes p53 as well as HIPK2 interesting targets for cancer therapy. Hence, understanding the role of HIPK2 as p53 activator may provide important insights in the process of tumor progression, and may also serve as the crucial point in the diagnostic and therapeutical aspects of cancer.

show abstract

Section: Hipk2 Phosphorylates P53 At Ser46 and Mediates Apoptosismentioning

confidence: 99%

Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Some insights into this decision-making process come from the isolation and characterization of p53 regulators such as ASPP1, ASPP2, 20 JMY 21 and TP53INP1(also named p53DINP1 and SIP). 22 These proteins direct p53 to specifically favor the activation of proapoptotic target genes over growth arrest-related target genes. They are, therefore, considered to be proapoptotic cofactors of p53.…”

Section: Introductionmentioning

confidence: 99%

“…21 The net effect of this is that JMY promotes the induction of apoptosis, but not cell-cycle arrest by p53. 21 Tumor suppressor p53-induced nuclear protein 1 (TP53INP1) was cloned independently from human and mouse cells, and was named p53DINP1 22 and SIP 25 , respectively. TP53INP1 was shown to be a p53-regulated gene.…”

Section: Introductionmentioning

confidence: 99%

“…22,26 The TP53INP1 protein interacts with p53 27 and with a kinase that phosphorylates p53 on serine 46, 22,27 thereby inducing phosphorylation of p53 at this site. 22 This modified p53 plays a pivotal role in apoptotic signaling, mainly through regulating the transcriptional activation of p53AIP1, an important mediator of p53-dependent apoptosis. 22 Indeed, ectopic expression of TP53INP1 triggers apoptosis 25 and enhances p53-induced apoptosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Novel link between E2F and p53: proapoptotic cofactors of p53 are transcriptionally upregulated by E2F

et al. 2005

View full text Add to dashboard Cite

The E2F1 transcription factor is a critical downstream target of the tumor suppressor RB. When activated, E2F1 induces cell proliferation. In addition, E2F1 can induce apoptosis via both p53-dependent and p53-independent pathways. A number of E2F-regulated genes, including ARF, ATM and Chk2, contribute to E2F-induced p53 stabilization. However, it is not known how E2F directs p53 activity towards apoptosis rather than growth arrest. We show that E2F1 upregulates the expression of four proapoptotic cofactors of p53 -ASPP1, ASPP2, JMY and TP53INP1 -through a direct transcriptional mechanism. Adenovirus E1A protein also induces upregulation of these genes, implicating endogenous E2F in this effect. TP53INP1 was shown to mediate phosphorylation of p53 on serine 46. We demonstrate that activation of E2F1 leads to phosphorylation of p53 on serine 46 and this modification is important for E2F1-p53 cooperation in apoptosis. Overall, these data provide novel functional links between RB/E2F pathway and p53-induced apoptosis.

show abstract

“…p53 is activated in response to various cellular stresses. Initially, kinases (such as ATM, 83,84 CHK2 85 and CKII 86 ) sense the stresses, and then phosphorylate the p53 protein at various sites (such as Ser15, Ser20 and Ser46) through interactions with cofactors (such as p53DINP1, 87 JMY 88 and ASPP 89 ). These upstream molecules modify the p53 protein, leading to the activation of p53.…”

Section: Tumor Suppressor P53 and Apoptosismentioning

confidence: 99%

p53, apoptosis and axon-guidance molecules

Arakawa¹

2005

Cell Death Differ

View full text Add to dashboard Cite

The p53 tumor-suppressor gene regulates apoptosis through the transcriptional activation of its target genes. The expression of the axon-guidance molecule UNC5B (also designated p53RDL1), which is a receptor for netrin-1, is directly regulated by p53. In the absence of netrin-1, UNC5B mediates p53-dependent apoptosis. Conversely, in the presence of netrin-1, p53-induced apoptosis is inhibited through the signaling pathway activated by the interaction between netrin-1 and UNC5B. A number of other molecules that are involved in axon guidance are inactivated in human cancers and are also regulated by p53. These findings suggest a close link between axon-guidance molecules and tumorigenesis.

show abstract

p53DINP1, a p53-Inducible Gene, Regulates p53-Dependent Apoptosis

Cited by 312 publications

References 26 publications

Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells

Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells

Novel link between E2F and p53: proapoptotic cofactors of p53 are transcriptionally upregulated by E2F

p53, apoptosis and axon-guidance molecules

Contact Info

Product

Resources

About