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Biomedical subjects

X Wu

Publications and source records attributed to X Wu.

At least 109 records · Page 6Linked to original sources
PubMed2001

The highly reduced genome of an enslaved algal nucleus.

Chromophyte algae differ fundamentally from plants in possessing chloroplasts that contain chlorophyll c and that have a more complex bounding-membrane topology. Although chromophytes are known to be evolutionary chimaeras of a red alga and a non-photosynthetic host, which gave rise to their exceptional membrane complexity, their cell biology is poorly understood. Cryptomonads are the only chromophytes that still retain the enslaved red algal nucleus as a minute nucleomorph. Here we report complete sequences for all three nucleomorph chromosomes from the cryptomonad Guillardia theta. This tiny 551-kilobase eukaryotic genome is the most gene-dense known, with only 17 diminutive spliceosomal introns and 44 overlapping genes. Marked evolutionary compaction hundreds of millions of years ago eliminated nearly all the nucleomorph genes for metabolic functions, but left 30 for chloroplast-located proteins. To allow expression of these proteins, nucleomorphs retain hundreds of genetic-housekeeping genes. Nucleomorph DNA replication and periplastid protein synthesis require the import of many nuclear gene products across endoplasmic reticulum and periplastid membranes. The chromosomes have centromeres, but possibly only one loop domain, offering a means for studying eukaryotic chromosome replication, segregation and evolution.

Base Sequence↗
PubMed2001

[A bivalent VP1 gene vaccine against Coxsackie virus B1/B3].

OBJECTIVE: To construct a bivalent VP1 gene vaccine against Coxsackie virus B1 and B3 (CVB1 and CVB3) and to test its immunogenicity in mice. METHODS: The VP1 gene of CVB1 was amplified by RT-PCR. The VP1 genes of CVB1 and of CVB3 under the control of cytomegalovirus (CMV) promoter and SV40 promoter respectively were inserted oppositely into the pCR3-Uni, a eukaryotic expression vector. The resultant bivalent gene vaccine plasmid was used to inoculate 3-week-old BALB/c mice. Immunofluorescence test and RT-PCR were conducted 24, 48, and 96 hours after the transfection. Sera of the tested animals were sampled at 0, 2, 4, and 6 weeks after the inoculation and detected for CVB-specific antibodies by ELISA. RESULTS: A bivalent gene vaccine plasmid of CVB1 and CVB3 was obtained. Samples of 4 and 6 weeks after the inoculation were shown to be CVB-antibody positive, while those of 0 and 2 weeks after the inoculation shown negative. CONCLUSION: The gene vaccine thus constructed induces CVB-speicific antibodies in mice, and can serve as gene vaccine candidate for human beings.

Animals↗
PubMed2001

Substrate-specific inhibition of RecQ helicase.

The RecQ helicases constitute a small but highly conserved helicase family. Proteins in this family are of particular interest because they are critical to maintenance of genomic stability in prokaryotes and eukaryotes. Eukaryotic RecQ helicase family members have been shown to unwind not only DNA duplexes but also DNAs with alternative structures, including structures stabilized by G quartets (G4 DNAs). We report that Escherichia coli RecQ can also unwind G4 DNAs, and that unwinding requires ATP and divalent cation. RecQ helicase is comparably active on duplex and G4 DNA substrates, as measured by direct comparison of protein activity and by competition assays. The porphyrin derivative, N-methyl mesoporphyrin IX (NMM), is a highly specific inhibitor of RecQ unwinding activity on G4 DNA but not duplex DNA: the inhibition constant (K(i)) for NMM inhibition of G4 DNA unwinding is 1.7 microM, approximately two orders of magnitude below the K(i) for inhibition of duplex DNA unwinding (>100 microM). NMM may therefore prove to be a valuable compound for substrate-specific inhibition of other RecQ family helicases in vitro and in vivo.

Adenosine Triphosphatases↗
PubMed2001

SMRTE inhibits MEF2C transcriptional activation by targeting HDAC4 and 5 to nuclear domains.

The silencing mediator for retinoic acid and thyroid hormone receptors (SMRT) mediates transcriptional repression by recruiting histone deacetylases (HDACs) to the DNA-bound nuclear receptor complex. The full-length SMRT (SMRTe) contains an N-terminal sequence that is highly conserved to the nuclear receptor corepressor N-CoR. To date, little is known about the activity and function of the full-length SMRTe protein, despite extensive studies on separated receptor interaction and transcriptional repression domains. Here we show that SMRTe inhibits MEF2C transcriptional activation by targeting selective HDACs to unique subnuclear domains. Indirect immunofluorescence studies with anti-SMRTe antibody reveal discrete cytoplasmic and nuclear speckles, which contain RARalpha in an RA-sensitive manner. Formation of the SMRTe nuclear speckles results in recruitment of several class I and class II HDACs to these subnuclear domains in a process depending on HDAC enzymatic activity. Intriguingly, although HDAC4 is located primarily in the cytoplasm, coexpression of SMRTe dramatically translocates HDAC4 from the cytoplasm into the nucleus, where HDAC4 prevents MEF2C from activating muscle differentiation. SMRTe also translocates HDAC5 from diffusive nucleoplasm into discrete nuclear domains. Accordingly, SMRTe synergizes with HDAC4 and 5 to inhibit MEF2C transactivation of target promoter, suggesting that nuclear domain targeting of HDAC4/5 may be important in preventing muscle cell differentiation. These results highlight an unexpected new function of the nuclear receptor corepressor SMRTe for its role in regulating cellular trafficking of nuclear receptor and selective HDACs that may play an important role in regulation of cell growth and differentiation.

Active Transport, Cell Nucleus↗
PubMed2001

The triple threat to nascent apolipoprotein B. Evidence for multiple, distinct degradative pathways.

We previously showed that Omega-3 fatty acids reduce secretion of apolipoprotein B (apoB) from cultured hepatocytes by stimulating post-translational degradation. In this report, we now characterize this process, particularly in regard to the two known processes that degrade newly synthesized apoB, endoplasmic reticulum (ER)-associated degradation and re-uptake from the cell surface. First, we found that Omega-3-induced degradation preferentially reduces the secretion of large, assembled apoB-lipoprotein particles, and apoB polypeptide length is not a determinant. Second, based on several experimental approaches, ER-associated degradation is not involved. Third, re-uptake, the only process known to destroy fully assembled nascent lipoproteins, was clearly active in primary hepatocytes, but Omega-3-induced degradation of apoB continued even when re-uptake was blocked. Cell fractionation showed that Omega-3 fatty acids induced a striking loss of apoB100 from the Golgi, while sparing apoB100 in the ER, indicating a post-ER process. To determine the signaling involved, we used wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, which blocked most, if not all, of the Omega-3 fatty acid effect. Therefore, nascent apoB is subject to ER-associated degradation, re-uptake, and a third distinct degradative pathway that appears to target lipoproteins after considerable assembly and involves a post-ER compartment and PI3K signaling. Physiologic, pathophysiologic, and pharmacologic regulation of net apoB secretion may involve alterations in any of these three degradative steps.

Androstadienes↗
PubMed2001

Expression profiling suggested a regulatory role of liver-enriched transcription factors in human hepatocellular carcinoma.

By using a cDNA array representing 14,000 cDNA clusters, we studied the expression profiles in paired clinical hepatocellular carcinoma (HCC) samples and the distal nontumorous liver tissues from the same patients. Despite the significant heterogeneity among the clinical samples, 72 genes (including 30 novel genes) were down-regulated and 84 genes (including 48 novel genes) were up-regulated in >50% of the cancer samples that were identified. The alterations in gene expression levels were confirmed by Northern blot and reverse-transcription PCR in all of 4 randomly selected genes. It was conspicuous that 21 of 38 hepatocarcinoma (HCC) down-regulated genes studied previously were reportedly regulated by a group of liver-enriched transcription factors (LETFs), and 12 of 36 HCC up-regulated genes studied previously were involved in protein translation. Reexamination of the cDNA array data further revealed that most of the genes known to be regulated by LETFs were down-regulated in at least a portion of the HCC samples. Among the LETFs, the expression level of CCAAT/enhancer-binding protein (C/EBP) alpha was down-regulated in cancer, whereas hepatocyte nuclear factor 1 (HNF-1), HNF-3beta, HNF-4alpha, and HNF-4gamma were up-regulated. The expression profiling thus suggested multiple regulatory pathways involved in HCC, especially that related to LETFs.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗
PubMed2001

The human homologue of the yeast DNA repair and TFIIH regulator MMS19 is an AF-1-specific coactivator of estrogen receptor.

Steroid/nuclear hormone receptors are ligand-dependent transcriptional regulators that control gene expression in a wide array of biological processes. The transcriptional activity of the receptors is mediated by an N-terminal ligand-independent transcriptional activation function AF-1 and a C-terminal ligand-dependent transcriptional activation function AF-2. The nuclear receptor coactivator RAC3 (also known as AIB1/ACTR/pCIP/TRAM-1/SRC-3) is amplified in breast cancer cells, where it forms a complex with estrogen receptor (ER) and enhances AF-2 activity of the receptor. Here, we identify a putative human homologue of the yeast DNA repair and transcriptional regulator MMS19 as a RAC3-interacting protein. The human MMS19 interacts with the N-terminal PAS-A/B domain of RAC3 in vivo and in vitro through a conserved C-terminal domain. Interestingly, the human MMS19 also interacts with estrogen receptors in a ligand-independent manner but not with retinoic acid receptor or thyroid hormone receptor. Overexpression of the interacting domain of hMMS19 strongly inhibits ER-mediated transcriptional activation, indicating a dominant negative activity. In contrast, over expression of the full-length hMMS19 enhances ER-mediated transcriptional activation. We find that hMMS19 stimulates the AF-1 activity of ERalpha, but not the AF-2 activity, suggesting that hMMS19 may be an AF-1-specific transcriptional coactivator of estrogen receptor.

Amino Acid Sequence↗
PubMed2001

Molecular modeling studies of the Akt PH domain and its interaction with phosphoinositides.

The serine-threonine protein kinase Akt is a direct downstream target of phosphatidylinositol 3-kinase (PI3-K). The PI3-K-generated phospholipids regulate Akt activity via directly binding to the Akt PH domain. The binding of PI3-K-generated phospholipids is critical to the relocalization of Akt to the plasma membrane, which plays an important role in the process of Akt activation. Activation of the PI3-K/Akt signaling pathway promotes cell survival. To elucidate the structural basis of the interaction of PI3-K-generated phospholipids with the Akt PH domain with the objective of carrying out structure-based drug design, we modeled the three-dimensional structure of the Akt PH domain. Comparative modeling-based methods were employed, and the modeled Akt structure was used in turn to construct structural models of Akt in complex with selected PI3-K-generated phospholipids using the computational docking approach. The model of the Akt PH domain consists of seven beta-strands forming two antiparallel beta-sheets capped by a C-terminal alpha-helix. The beta1-beta2, beta3-beta4, and beta6-beta7 loops form a positively charged pocket that can accommodate the PI3-K-generated phospholipids in a complementary fashion through specific hydrogen-bonding interactions. The residues Lys14, Arg25, Tyr38, Arg48, and Arg86 form the bottom of the binding pocket and specifically interact with the 3- and 4-phophate groups of the phospholipids, while residues Thr21 and Arg23 are situated at the wall of the binding pocket and bind to the 1-phosphate group. The predicted binding mode is consistent with known site-directed mutagenesis data, which reveal that mutation of these crucial residues leads to the loss of Akt activity. Moreover, our model can be used to predict the binding affinity of PI3-K-generated phospholipids and rationalize the specificity of the Akt PH domain for PI(3,4)P2, as opposed to other phospholipids such as PI(3)P and PI(3,4,5)P3. Taken together, our modeling studies provide an improved understanding of the molecular interactions present between the Akt PH domain and the PI3-K-generated phospholipids, thereby providing a solid structural basis for the design of novel, high-affinity ligands useful in modulating the activity of Akt.

Amino Acid Sequence↗
PubMed2001

Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function.

The NUP98 gene encodes precursor proteins that generate two nucleoplasmically oriented nucleoporins, NUP98 and NUP96. By using gene targeting, we have selectively disrupted the murine NUP98 protein, leaving intact the expression and localization of NUP96. We show that NUP98 is essential for mouse gastrulation, a developmental stage that is associated with rapid cell proliferation, but dispensable for basal cell growth. NUP98-/- cells had an intact nuclear envelope with a normal number of embedded nuclear pore complexes. Typically, NUP98-deficient cells contained on average approximately 5-fold more cytoplasmic annulate lamellae than control cells. We found that a set of cytoplasmically oriented nucleoporins, including NUP358, NUP214, NUP88, and p62, assembled inefficiently into nuclear pores of NUP98-/- cells. Instead, these nucleoporins were prominently associated with the annulate lamellae. By contrast, a group of nucleoplasmically oriented nucleoporins, including NUP153, NUP50, NUP96, and NUP93, had no affinity for annulate lamellae and assembled normally into nuclear pores. Mutant pores were significantly impaired in transport receptor-mediated docking of proteins with a nuclear localization signal or M9 import signal and showed weak nuclear import of such substrates. In contrast, the ability of mutant pores to import ribosomal protein L23a and spliceosome protein U1A appeared intact. These observations show that NUP98 disruption selectively impairs discrete protein import pathways and support the idea that transport of distinct import complexes through the nuclear pore complex is mediated by specific subsets of nucleoporins.

Active Transport, Cell Nucleus↗
PubMed2001

A new phenoxyacetate-based linker system for the solid-phase synthesis of oligosaccharides.

[structure: see text]. A novel linker system has been designed, and its first application to solid-phase oligosaccharide synthesis is described. The use of the highly reactive o-nitro-phenoxyacetate linker allows a fast and quantitative cleavage using mild basic conditions. This method combined with the trichloroacetimidate glycosylation exhibits highly promising results as demonstrated for the synthesis of tetrasaccharide 1 (n = 3) containing glucose beta(1 --> 4) and beta(1 --> 6) linkages.

Carbohydrate Sequence↗
PubMed2001

Enantioselective metabolism of propanolol in isolated hepatocytes prepared from untreated, PB- or 3-MC-pretreated rats.

The present paper describes the metabolism of a chiral drug propranolol (PL) using isolated hepatocytes freshly prepared from untreated, PB- or 3-MC-pretreated rats. In order to examine not only the existence of enantioselectivity but also the effect of enzyme inducer (PB or 3-MC) on PL metabolism, 500 microM PL (RS-PL, R(+)-PL or S(-)-PL) was incubated at 37 degrees C using 8 x 10(6) cells/ml isolated rat hepatocytes. Then, the elimination amount of PL and the formation amounts of eight kinds of the metabolites including ring hydroxylated metabolites (4-OH-, 5-OH- and 7-OH-PL) and side chain metabolites (NDP, AcNDP, PGL, NLA and NAA) were simultaneously determined by HPLC. By 3-MC- and PB-pretreatment, a significant increase was noticed in PL elimination and also in the formation of PL metabolites, NDP, NLA and NAA. Furthermore, the presence of enantioselectivity was observed, i.e. the substrate R(+)-PL was always eliminated faster than the substrate S(-)-PL. Regarding the metabolite formation, NDP, AcNDP and NAA were dominantly produced from R(+)-PL, and NLA, PGL and the ring hydroxylated metabolites from S(-)-PL. In all cases of PL elimination and the metabolite formation, the amounts of the metabolites derived from RS-PL indicated the mean values of the respective amounts derived from R(+)-PL and S (-)-PL. Using the three kinds of isolated rat hepatocytes mentioned above, the kinetic parameters of NDP-formation at 37 degrees C for 10 min were calculated using RS-PL, R(+)-PL or S(-)-PL as a substrate. From the pseudo values of V'max/K'm (microliter/min.8 x 10(6) cells), the easiest formation of NDP from R(+)-PL was observed in the rat hepatocyte system pretreated with 3-MC.

Animals↗
PubMed2001

Defective granule exocytosis in Rab27a-deficient lymphocytes from Ashen mice.

Because mutations in Rab27a have been linked to immune defects in humans, we have examined cytotoxic lymphocyte function in ashen mice, which contain a splicing mutation in Rab27a. Ashen cytotoxic T lymphocytes (CTLs) showed a >90% reduction in lytic activity on Fas-negative target cells compared with control C3H CTLs, and ashen natural killer cell activity was likewise diminished. Although their granule-mediated cytotoxicity pathway is profoundly defective, ashen CTLs displayed a normal FasL-Fas cytotoxicity pathway. The CD4/8 phenotype of ashen T cells and their proliferative responses were similar to controls. Ashen CTLs had normal levels of perforin and granzymes A and B and normal-appearing perforin-positive granules, which polarized upon interaction of the CTLs with anti-CD3-coated beads. However, rapid anti-CD3-induced granule secretion was drastically defective in both CD8(+) and CD4(+) T cells from ashen mice. This defect in exocytosis was not observed in the constitutive pathway, as T cell receptor-stimulated interferon-gamma secretion was normal. Based on these results and our demonstration that Rab27a colocalizes with granzyme B-positive granules and is undetectable in ashen CTLs, we conclude that Rab27a is required for a late step in granule exocytosis, compatible with current models of Rab protein function in vesicle docking and fusion.

Abatacept↗
PubMed2001

Response of human DNA polymerase iota to DNA lesions.

Lesion bypass is an important mechanism to overcome replication blockage by DNA damage. Translesion synthesis requires a DNA polymerase (Pol). Human Pol iota encoded by the RAD30B gene is a recently identified DNA polymerase that shares sequence similarity to Pol eta. To investigate whether human Pol iota plays a role in lesion bypass we examined the response of this polymerase to several types of DNA damage in vitro. Surprisingly, 8-oxoguanine significantly blocked human Pol iota. Nevertheless, translesion DNA synthesis opposite 8-oxoguanine was observed with increasing concentrations of purified human Pol iota, resulting in predominant C and less frequent A incorporation opposite the lesion. Opposite a template abasic site human Pol iota efficiently incorporated a G, less frequently a T and even less frequently an A. Opposite an AAF-adducted guanine, human Pol iota was able to incorporate predominantly a C. In both cases, however, further DNA synthesis was not observed. Purified human Pol iota responded to a template TT (6-4) photoproduct by inserting predominantly an A opposite the 3' T of the lesion before aborting DNA synthesis. In contrast, human Pol iota was largely unresponsive to a template TT cis-syn cyclobutane dimer. These results suggest a role for human Pol iota in DNA lesion bypass.

Acetoxyacetylaminofluorene↗
PubMed2001

Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients.

Sequence variations have been identified in a number of DNA repair genes, including XPD, but the effect of these polymorphisms on DNA repair capacity (DRC) is uncertain. We therefore examined XPD polymorphisms at Lys751Gln and Asp312Asn in 341 white lung cancer cases and 360 age-, sex-, ethnicity-, and smoking-matched controls accrued in a hospital-based molecular epidemiological study of susceptibility markers for lung cancer. As previously reported, DRC was statistically significantly lower in the cases than in the controls (7.8% versus 9.5%; P < 0.001), which represents an average 18% reduction among the cases. The variant Lys751Gln and Asp312Asn allele frequencies were 0.36 and 0.29, respectively, for the cases and 0.33 and 0.27, respectively, for the controls. For subjects homozygous for the variant genotype at either locus, the adjusted odds ratio [95% confidence interval (CI)] was 1.84 (1.11-3.04; P = 0.018, for trend). Both cases and controls with the wild-type genotypes exhibited the most proficient DRC. The risk (95% CI) for suboptimal DRC (defined as less than the median DRC value among the controls) was 1.57 (0.74-3.35) for those with the Gln/Gln751 genotype. For cases with the Asn/Asn312 genotype, the risk (95% CI) was 3.50 (1.06-11.59). For cases who were homozygous at either locus, the risk was 2.29 (1.03-5.12; P = 0.048, for trend). The pattern was less evident among the controls, although there was a nonsignificant 41% increase in the risk of suboptimal DRC for controls who were homozygous at either locus. These results suggest that the two XPD polymorphisms have a modulating effect on DRC, especially in the cases.

Case-Control Studies↗
PubMed2001

[Fourier analysis of macular local electroretinogram in retinal detachment].

OBJECTIVE: To understand the sites and physiological characteristics of macular dysfunction in retinal detachment (RD) by evaluating fundamental harmonic (1f) and second harmonic (2f) components of flicker local electroretinogram (LERG). METHODS: LERG were recorded in 128 eyes of 120 patients to a flicker sinusoidally to 31Hz with a hand-held stimulator with direct visualization of the fundus through dilated pupils. RESULTS: Compared to controls, patients showed losses of both fundamental and second harmonic amplitudes. The abnormality rates of fundamental amplitude in groups with RD affected time < 1 weeks, 1 approximately weeks, 2 approximately weeks, 4 approximately weeks and > 8 weeks were 15%, 25%, 47%, 76% and 91% respectively; and the abnormality of rates fundamental-second harmonic amplitude ratios (1f/2f) were 5%, 14%, 28%, 64% and 87% respectively. On average, 2f decreased more quikly than 1f and 1f/2f tended to increase with the course of disease. The results show both 1f and 2f descend in the RD eyes with or no macular detachment (P < 0.05). 2f just descend obviously in the 48 macular detachment eyes (P < 0.01), so that 1f/2f ascend in these eyes(P < 0.05). There was a significant relation between amplitudes of LERG in the detached eyes before surgery and best postoperational correct vision in the attached eyes. CONCLUSION: In the eyes with retinal detachment, both receptoral and postreceptoral sites contribute to macular dysfunction. The level of macular dysfunction in the eyes with or no macular detachment is different. It would be of clinical value to obtain a fundamental-second harmonic ratio in order to assess the disturbance in the different site of macular. In our opinion: macular flicker local electroretinogram is an important indicator of prognosis to the functional recovery of the attached eye after corrective surgery.

Adolescent↗
PubMed2001

Radiation-induced chromatid breaks as a predictor of breast cancer risk.

PURPOSE: In in vivo models, radiation-induced genomic instability correlates with the risk of breast cancer development. In addition, homozygous mutations in tumor suppressor genes associated with breast cancer development adversely affects the processing and repair of radiation-induced DNA damage. We performed a case-control study to determine whether an assay measuring radiation-induced chromatid breaks correlated with the risk of having bilateral breast cancer. METHODS AND MATERIALS: Patients were prospectively studied on an institutional review board-approved protocol. We included only women with bilateral breast cancer as cases to obtain patients with a presumed genetic susceptibility for breast cancer. Controls were healthy women without a previous cancer history. A mutagen sensitivity assay using gamma-radiation was performed on lymphocytes obtained from 26 cases and 18 controls. One milliliter of whole blood was cultured with 9 mL of blood medium for 91 h and then treated with 125 cGy using a Cs-137 irradiator. Following an additional 4 h in culture, cells were treated with Colcemid for 1 h to arrest cells in metaphase. The number of chromatid breaks per cell was counted using a minimum of 50 metaphase spreads for each sample. RESULTS: Cases had a statistically higher number of gamma-radiation-induced chromatid breaks per cell than controls, with mean values of 0.61 +/- 0.24 vs. 0.45 +/- 0.14, respectively (p = 0.034, Wilcoxon rank sum test). Using the 75th percentile value in the control group as a definition of radiation sensitivity, the radiation-sensitive individuals had a 2.83-fold increased odds ratio for breast cancer development compared with individuals who were not radiation sensitive (95% confidence intervals of 0.83 and 9.67). CONCLUSIONS: These preliminary data suggest that sensitivity to radiation-induced chromatid breaks in lymphocytes correlates with the risk of bilateral breast cancer. Although the differences between cases and controls were statistically significant, the small sample size necessitates that this finding be validated in a larger study. More data are also needed to determine whether this sensitivity is limited to breast cancer patients with a genetic susceptibility for the disease or also applies to the general breast cancer population.

Adult↗
PubMed2001

Stabilization and activation of p53 by the coactivator protein TAFII31.

Regulation of the stability of p53 is key to its tumor-suppressing activities. mdm2 directly binds to the amino-terminal region of p53 and targets it for degradation through the ubiquitin-proteasome pathway. The coactivator protein TAF(II)31 binds to p53 at the amino-terminal region that is also required for interaction with mdm2. In this report, we demonstrate that expression of TAF(II)31 inhibits mdm2-mediated ubiquitination of p53 and increases p53 levels. TAF(II)31-mediated p53 stabilization results in activation of p53-mediated transcriptional activity and leads to p53-dependent growth arrest in fibroblasts. UV-induced stabilization of p53 coincides with an increase in p53-associated TAF(II)31 and a corresponding decrease in mdm2-p53 interaction. Non-p53 binding mutant of TAF(II)31 fails to stabilize p53. Our results suggest that direct interaction of TAF(II)31 and p53 not only mediates p53 transcriptional activation but also protects p53 from mdm2-mediated degradation, thereby resulting in activation of p53 functions.

3T3 Cells↗