Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Type of study
Language
Publication year range
1.
Biochem Biophys Res Commun ; 424(3): 427-32, 2012 Aug 03.
Article in English | MEDLINE | ID: mdl-22766506

ABSTRACT

Pax6 is a member of the Pax family of transcription factors that contains a DNA binding paired-box and homeobox domain. In animals, including humans, Pax6 plays a key role in development, regulating organogenesis of the eye and brain. The current data show that histone acetyltransferase Tip60 physically interacts with Pax6 in developing post-natal day 4 (P4) mouse retinas. We also found that Tip60 binds with paired-domain of Pax6 using its chromo- and zinc-finger-containing regions, and that these protein interactions were needed for the effective full-transcriptional activation of Pax6. Furthermore, among the combinations of Pax6-target gene interactions using its two DNA binding domain, paired- and homeobox domain, Tip60 significantly enhanced the transcriptional activity of Pax6 on the paired-domain binding sequence (P6CON) containing reporter construct (pCON) than other homeo domain and chimera binding containing pP3 and pCON/P3 constructs. Taken together, these results suggest that Tip60 binds with Pax6 and that this physical interaction leads to the full-transcriptional activation of Pax6 during retina development.


Subject(s)
Eye Proteins/metabolism , Gene Expression Regulation, Developmental , Histone Acetyltransferases/metabolism , Homeodomain Proteins/metabolism , Paired Box Transcription Factors/metabolism , Repressor Proteins/metabolism , Retina/growth & development , Trans-Activators/metabolism , Animals , HEK293 Cells , Humans , Lysine Acetyltransferase 5 , Mice , Mice, Inbred ICR , PAX6 Transcription Factor , Retina/enzymology , Transcription, Genetic , Transcriptional Activation
2.
FEBS Lett ; 582(19): 2826-32, 2008 Aug 20.
Article in English | MEDLINE | ID: mdl-18656471

ABSTRACT

The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses and can trigger apoptosis in many cell types, including neurons. In this study, we have shown that the Microtubule-Associated Protein 1B (MAP1B) light chain can interact with the tumor suppressor p53. We also demonstrate that both p53 and the MAP1B light chain (MAP1B-LC1) alter their localization from the cytoplasm to the nucleus when neuroblastoma cells, SH-SY5Y, are treated with doxorubicin. Additionally, we demonstrate that the MAP1B-LC1 negatively regulates p53-dependent transcriptional activity of a reporter construct driven by the p21 promoter. Consequently, MAP1B-LC1 binds to p53 and this interaction leads to the inhibition of doxorubicin-induced apoptosis in SH-SY5Y cells.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , Apoptosis , Doxorubicin/pharmacology , Microtubule-Associated Proteins/metabolism , Neuroblastoma/metabolism , Tumor Suppressor Protein p53/metabolism , Cell Line, Tumor , Cell Nucleus/metabolism , Cytoplasm/metabolism , Genes, Reporter , Humans , Luciferases/genetics , Neuroblastoma/genetics , Protein Structure, Tertiary , Protein Transport , Transcription, Genetic , Transcriptional Activation , Tumor Suppressor Protein p53/antagonists & inhibitors , Tumor Suppressor Protein p53/genetics
3.
Biochem Biophys Res Commun ; 373(1): 146-50, 2008 Aug 15.
Article in English | MEDLINE | ID: mdl-18555006

ABSTRACT

p73 and p53 have been known to play an important role in cellular damage responses such as apoptosis. Although p73 is a structural and functional homolog of p53 tumor suppressor gene, much less is known about the mechanism of p73-induced apoptotic cell death. In this study, we demonstrate that p19(ras) interaction with p73beta amplifies p73beta-induced apoptotic signaling responses including Bax mitochondrial translocation, cytochrome c release, increased production of reactive oxygen species (ROS) and loss of mitochondrial transmembrane potential (DeltaPsi(m)). Furthermore, endogenous expression of p19(ras) and p73beta is significantly increased by Taxol treatment, and Taxol-enhanced endogenous p73beta transcriptional activities are further amplified by p19(ras), which markedly increased cellular apoptosis in p53-null SAOS2 cancer cell line. These results have important implications for understanding the molecular events of p19(ras) to p73 functions in cancer cells.


Subject(s)
Apoptosis , DNA-Binding Proteins/metabolism , Mitochondria/metabolism , Neoplasms/metabolism , Nuclear Proteins/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Tumor Suppressor Proteins/metabolism , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cytochromes c/metabolism , Humans , Membrane Potential, Mitochondrial , Mitochondria/drug effects , Paclitaxel/pharmacology , Protein Transport , Reactive Oxygen Species/metabolism , Tumor Protein p73 , bcl-2-Associated X Protein/metabolism
4.
J Biol Chem ; 283(29): 20077-86, 2008 Jul 18.
Article in English | MEDLINE | ID: mdl-18499675

ABSTRACT

TIP60, a histone acetyl transferase, acts as a p53 coactivator by interfering with MDM2-mediated degradation of p53. However, little is known about its functional regulation of p73, which has structural features similar to p53. In this study we found that TIP60 represses apoptosis, which is induced by exogenous and endogenous p73beta. TIP60 also negatively regulated the expression of p73beta downstream target genes such as p21 and Bax. Moreover, the specific repression of p73beta-mediated transactivation by TIP60 was independent of p53 expression and not due to histone deacetylase recruiting transcriptional machinery. Transcriptional activities of both p73 splicing variants, p73alpha and p73beta, were also repressed by TIP60. Furthermore, TIP60 markedly enhanced p73beta binding affinity to MDM2 and physically associated with MDM2 through its zinc finger domain, which is specifically localized in the nucleus. Therefore, we demonstrate that TIP60 forms a ternary complex with p73beta, which is directly bridged by MDM2. It is important to note that our findings contribute to a functional linkage between TIP60 and p73beta through MDM2 in the transcriptional regulation of cellular apoptosis.


Subject(s)
DNA-Binding Proteins/metabolism , Histone Acetyltransferases/metabolism , Nuclear Proteins/metabolism , Proto-Oncogene Proteins c-mdm2/metabolism , Transcriptional Activation/genetics , Tumor Suppressor Proteins/metabolism , Active Transport, Cell Nucleus , Animals , Apoptosis , Cell Line , DNA-Binding Proteins/genetics , Down-Regulation , Histone Acetyltransferases/genetics , Humans , Lysine Acetyltransferase 5 , Mice , Nuclear Proteins/genetics , Promoter Regions, Genetic/genetics , Protein Binding , Proto-Oncogene Proteins c-mdm2/genetics , Signal Transduction , Tumor Protein p73 , Tumor Suppressor Proteins/genetics , bcl-2-Associated X Protein/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...