人们常常把肿瘤与癌症混为一谈，认为肿瘤就是癌症，癌症就是肿瘤，其实两者有根本的不同。肿瘤包括良性肿瘤和恶性肿瘤两类，恶性程度介于两者之间的又称为“交界瘤”，所以肿瘤不等于癌症。
恶性肿瘤共有1000多种，共分两大类，即癌与肉瘤。命名原则是根据发生部位和组织来源，在其名称后面加上“癌”字或“肉瘤”字样的均为恶性肿瘤。https://www.doczj.com/doc/3a14742143.html,/
生长于上皮组织的恶性肿瘤称为“癌”。所谓上皮组织，是指分布在人体表面和人体内所有的空腔脏器，如空腔、食管、胃、肠管等“的细胞，这些器官如有恶性肿瘤生长，则分别称为口腔癌、食管癌、胃癌、肠癌等。
凡是人体结缔组织如脂肪、肌肉、骨骼、淋巴、造血组织等发生的恶性肿瘤，统称为“肉瘤“，如脂肪肉瘤、平滑肌肉瘤、骨肉瘤、淋巴肉瘤等。https://www.doczj.com/doc/3a14742143.html,/html/exlblby/196.htm 人们常易把良性肿瘤和恶性的肉瘤的称呼相混淆，如脂肪瘤、平滑肌瘤等都是良性肿瘤。可是一旦在它们的名字间加上一个“肉”字，如脂肪肉瘤、纤维肉瘤等就是恶性肿瘤，别看是一字之差，却谬之千里，是良恶之分。所以，把肉瘤当成良性肿瘤就大错特错了。
另有一类来源于多种组织成分的恶性肿瘤，既不称癌也不叫肉瘤，而是在前面加上“恶性”两字，如恶性混合瘤等。凡是来自胚胎细胞或未
成熟组织的恶性肿瘤，均称为“母细胞瘤”，如肝母细胞瘤及髓母细胞瘤等。此外，还有少数恶性肿瘤仍然沿用习惯名称，如霍奇金病、非霍奇金病、白血病及黑色素瘤等。
因此，恶性肿瘤也不都叫“癌”。
良性肿瘤是指那些生长在体表或脏器内的生物，形似肿瘤，但不具备恶性肿瘤的生物学特征。https://www.doczj.com/doc/3a14742143.html,/
医学对良性肿瘤的命名原则是在发生部位名称后面加上一个“瘤”字，如发生在膀胱的肿瘤形状像乳头，就取名为“膀胱乳头状瘤”。若肿瘤来源于结缔组织就直接在组织名称后面加上“瘤”字，如纤维瘤、脂肪瘤及血管瘤等。正所谓良恶有别，不可混称。
另外，处于良恶性之间的肿瘤难以确定是真正的良性还是恶性，这第三种肿瘤，人们称之为“中间性肿瘤”，“交界性肿瘤”、“境界瘤”、“潜在恶性瘤”、“半恶性肿瘤”等，较多称之为“交界瘤”。交界瘤的特点：1）肿瘤细胞的形态介于良性、恶性之间，因此在病理学的诊断上存在分歧，临床上也形成两派，这正是它分化不典型的特性所在。2）生长方式上有局部扩散的倾向，常规按良性肿瘤做局部切除后往往容易局部复发，但却不发生转移，或极少有转移，或即使出现局部转移，仍然进展缓慢，对病人威胁不大。实际表现有局部扩散或偶有转移，或者细胞形态符合恶性，但没有明显的扩散转移等恶性表现。
恶性肿瘤通常生长迅速，呈浸润性生长，可破坏周围组织，无包膜或仅有假包膜，肿瘤分化差，组织及细胞形态与其相应的正常组织差甚远，显示异形性，排列扰乱，细胞核形状不规则，常有不同程度的深染，核仁增大增多，并出现病理性核分裂像；肿瘤内多出现继发性改变，如出血、坏死、囊性变及感染等。手术切除后常复发，并容易转移，对周围组织造成广泛破坏。如不及时治疗，常导致死亡。
https://www.doczj.com/doc/3a14742143.html,/cancer/html/naozhongliu/086177051.htm
癌与肉瘤的区分在临床上有很大的意义。癌多见于40岁以上的中老年人，淋巴系转移常见；而肉瘤则多发于年轻人，多见血行转移。
SUMO修饰蛋白在肿瘤防治中的机制研究
作者：钟颖， 江将， 韩昱晨
作者单位：钟颖,江将(中国医科大学90期七年制,沈阳,110001)， 韩昱晨(中国医科大学基础医学院病理教研室,沈阳,110001)
刊名：
实用药物与临床
英文刊名：SHIYONG PHARMACY AND CLINICAL REMEDIES
年，卷(期)：2009，12(1)
被引用次数：0次
参考文献(18条)
1.Watson IR.Irwin MS Ubiquitin and Ubiquitin-Like Modifications of the p53 family 2006
2.Herrmann J.Lerman LO.Lerman A Ubiquitin and UbiquitinLike Proteins in Protein Regulation 2007
3.Marinovic AC.Zheng B.Mitch WE Tissue-specific regulation of ubiquitin(VbC)transcription by glucocorticoids:in vivo and in vitro analyses 2007
4.Muller S.Hoege C.Pyrowolakis G SUMO,ubiquitin's mysterious cousin 2001
5.Itahana Y.Yeh ETH.Zhang Y Nucleocytoplasmic shuttling modulates activity and ubiquitination-dependent turnover of SUMO-specific protease 2 2006
6.Rodriguez MS.Dargemont C.Hay RT SUMO-1 conjugation in vivo requires both a consensus modification motif and nuclear targeting 2001
7.Xirodimas DP.Stephen https://www.doczj.com/doc/3a14742143.html,ne DP Cocompartmentalization of p53 and Mdm2 is a major determinant for Mdm 22 mediated degradation of p53 2001(01)
8.Grossman SR.Doato ME.Brignone C Polyubiquitination of p53 by a ubiquitin lignse activity of p300 2003(5617)
9.Lee MH.Lee SW.Lee EJ SUMO-specific protease SUSP4 positively regulates p53 by pormotin Mdm2 self-ubiquitination 2006(12)
10.Muller S.Ledl A.Schmidt D SUMO:a regulator of gene expression and genome integrity 2004(11)
11.Chen L.Chen J MDM22ARF complex regulates p53 sumoylation 2003(34)
12.Meng MV.Shinohara K.Grossfeld GD Significance of highgrade prostatic intraepithelial neoplasia on prostate biopsy 2003
13.Glass C.K & Rosenfeild MG The coregulator exchange in transcriptional functions of nuclear receptors 2006
14.Cheng JK.Bawa T.Lee P Role of desumoylation in the development of prostate Cancer 2006(08)
15.Jónsson ZO.Jha S.Wohlschlegel JA Rvblp/Rvb2p recruit Arp5p and assemble afunctional Ino80 chromatin remodeling complex 2004
16.Gallant P Control of transcripdon by pontin and reptin 2007(04)
17.Kim JH.Choi HJ.Kim B Roles of sumoylation of a reptin chromatin-remodelling complex in cancer metastasis 2006(08)
18.Alarcon-Vargas D.Ronai Z SUMO in cancer-wrestlers wanted 2002
p53 and repress p53 activity.
The activity of the p53 tumor suppressor protein and the c-Jun protooncogene is regulated by posttranslational modifications, such as phosphorylation or ubiquitination. In addition, covalent attachment of the ubiquitin-like modifier SUMO appears to modulate their transcriptional activity. Sumoylation proceeds via an enzymatic pathway that is mechanistically analogous to ubiquitination, but requires a different E1-activating enzyme and Ubc9, a SUMO-specific E2-conjugating enzyme. Here, we show that two members of the PIAS family, PIAS1 and PIASxbeta, act as specific E3-like ligases that promote sumoylation of p53 and c-Jun in vitro and in vivo. The PIAS proteins physically interact with both p53 and c-Jun. In addition, they bind to Ubc9, suggesting that they recruit the E2 enzyme to their respective substrate. The SUMO ligase activity requires the conserved zinc-finger domain, which is distantly related to the essential RING-finger motif, found in a subset of ubiquitin ligases. Furthermore, similar to RING-type ubiquitin ligases, PIASxbeta can catalyze its own modification. Hence, these data further extend the analogy between the ubiquitin and SUMO pathway. Strikingly, PIAS proteins strongly repress the transcriptional activity of p53, suggesting that the PIAS-SUMO pathway plays a crucial role in the regulation of p53 and presumably other transcription factors.
2.期刊论文卢星榕.易继林.LU Xing-rong.YI Ji-lin SUMO-1对p53基因诱导HepG2细胞凋亡的增强作用-中国普外
基础与临床杂志2005,12(4)
目的研究小分子泛素样修饰体-1(small ubiquitin-like modifier-1,SUMO-1在野生型p53基因诱导HepG2细胞凋亡中的作用.方法用含人野生型p53基因质粒pcDNA3-wtp53(pwtp53)、含人双微粒体基因2[(human double minute gene 2(HDM2);鼠同源基因为MDM2]质粒pCMV-HDM1B(pMDM2)、含人SUMO-1基因质粒pcDNA3-His6-SUMO-1(pSUMO-1)和空质粒pcDNA3分别或同时转染HepG2细胞,获得各转染细胞系,应用Western blot检测转染后细胞中质粒蛋白的表达及流式细胞技术检测细胞凋亡比例.结果转染pwtp53和pMDM2质粒的HepG2细胞均可见p53及MDM2蛋白条带,同时转染pSUMO-1质粒的细胞分别可见被SUMO-1修饰的相对分子量较大的p53和MDM2蛋白条带,在未转染任何质粒、仅转染空质粒和pSUMO-1质粒的细胞中只检测到少量p53蛋白表达.转染pwtp53及
pwtp53+pSUMO-1质粒的HepG2细胞凋亡比例分别为(16.79士1.62)%和(18.15±1.36)%,转染pwtp53+pMDM2+pSUMO-1质粒的细胞凋亡比例为
(14.06±1.84)%,转染pwtp53+pMDM2质粒的细胞凋亡比例则下降至(5.17士1.23)%,与前三者比较差异有显著性意义(P＜0.01);其他转染系细胞中的细胞凋亡比例均≤2%,差异无显著性意义.结论 SUMO-1通过与p53蛋白的结合或翻译后修饰,抑制MDM2等癌基因蛋白对p53蛋白的降解,可增强p53抑癌基因诱导的细胞凋亡.
3.外文期刊Muller.S.Berger.M.Lehembre.F.Seeler.JS.Haupt.Y.Dejean.A c-Jun and p53 activity is
modulated by SUMO-1 modification.
The ubiquitin-related SUMO-1 molecule has been shown recently to modify covalently a number of cellular proteins including IkappaBalpha. SUMO-1 modification was found to antagonize IkappaBalpha ubiquitination and protect it from degradation. Here we identify the transcription factors c-Jun and p53, two well known targets of ubiquitin, as new substrates for SUMO-1 both in vitro and in vivo. In contrast to ubiquitin, SUMO-1 preferentially targets a single lysine residue in c-Jun (Lys-229), and the abrogation of SUMO-1 modification does not compromise its ubiquitination. Activation of Jun NH(2)-terminal kinases, which induces a reduction in c-Jun ubiquitination, similarly decreases SUMO-1 modification. Accordingly, loss of the two major Jun NH(2)-terminal kinase phosphorylation sites in c-Jun, Ser-63 and Ser-73, greatly enhances conjugation by SUMO-1. A SUMO-1- deficient c-JunK229R mutant shows an increased transactivation potential on an AP-1-containing promoter compared with wild-type c-Jun, suggesting that SUMO-1 negatively regulates c-Jun activity. As with c-Jun, SUMO-1 modification of p53 is abrogated by phosphorylation but remains unaltered upon chemical damage to DNA or Mdm2-mediated ubiquitination. The SUMO-1 attachment site in p53 (Lys-386) resides within a region known to regulate the DNA binding activity of the protein. A p53 mutant, defective for SUMO-1 conjugation, shows unaltered ubiquitination but has a slightly impaired apoptotic activity, indicating that modification by SUMO-1 might be important for the full biological activity of p53. Taken together, these data provide a first link between the SUMO-1 conjugation pathway and the regulation of transcription factors.
4.外文期刊Li.T.Santockyte.R.Shen.RF.Tekle.E.Wang.G.Yang.DC.Chock.PB Expression of SUMO-2/3 induced
senescence through p53- and pRB-mediated pathways.
Three highly homologous small ubiquitin-related modifier (SUMO) proteins have been identified in mammals. Modifications of proteins by SUMO-1 have been shown to regulate transcription, nucleocytoplasmic transport, protein stability, and protein-protein interactions. Relative to SUMO-1, little is known about the functions of SUMO-2 or SUMO-3 (referred to as SUMO-2/3). Here, stable
cell lines overexpressing processed forms of SUMO-2/3 (SUMO-2/3GG) as well as their non-conjugatable derivatives, SUMO-2/3DeltaGG, were established. Cells overexpressing SUMO-2/3GG showed a premature senescence phenotype as revealed by cellular morphology and senescence-associated galactosidase activity. The senescence pathway protein p21 was up-regulated in cells overexpressing SUMO-2/3GG. In contrast, cells overexpressing non-conjugatable forms of SUMO-2/3DeltaGG showed neither an apparent senescent phenotype nor elevated p21. Both p53 and pRB were found to be modified by SUMO-2/3. Site-directed mutagenesis studies showed that Lys-386 of p53, the SUMO-1 modification site, is also the modification site for SUMO-2/3. In addition, H2O2 treatment of untransfected cells caused an increase in p53 sumoylation by SUMO-2/3, whereas that by SUMO-1 remained unchanged. Moreover, knocking down tumor suppressor proteins p53 or pRB using small interfering RNA significantly alleviated the premature senescence phenotypes in SUMO-2/3GG overexpressing cells. Together, our results reveal that p53 and pRB can be sumoylated by SUMO-2/3 in vivo, and such modification of
p53 and pRB may play roles in premature senescence and stress response.
5.外文期刊Kwek.SS.Derry.J.Tyner.AL.Shen.Z.Gudkov.AV Functional analysis and intracellular
localization of p53 modified by SUMO-1.
p53 tumor suppressor is a subject of several post-translational modifications, including phosphorylation, ubiquitination and acetylation, which regulate p53 function. A new covalent modification of p53 at lysine 386 by SUMO-1 was recently identified. To elucidate the function of sumoylated p53, we compared the properties of wild type p53 and sumoylation-deficient p53 mutant, K386R. No differences were found between wild type p53 and K386R mutant of p53 in transactivation or growth suppression assays. Moreover, overexpression of SUMO-1 has no effect on p53-regulated transcription. Biochemical fractionation showed that sumoylated p53 is localized in the nucleus and is tightly bound to chromatin structures. p53 and SUMO-1 co-localized in PML nuclear bodies in 293 cells and the nucleoli in MCF7 and HT1080 cells. However, sumoylation-deficient p53 mutant showed a similar pattern of intranuclear localization, suggesting that SUMO-1 does not target p53 to subnuclear structures. These data indicate that SUMO-1 modification of
p53 at lysine 386 may not be essential for p53's cellular localization, transcriptional activation, or growth regulation.
6.外文期刊Berta. MA.Mazure. N.Hattab. M.Pouyssegur. J.Brahimi-Horn. MC SUMOylation of hypoxia-
factor (HIF). Here, we show that HIF-1 alpha undergoes post-translational modification by the three isoforms of the small ubiquitin-related modifier (SUMO-1, -2 and -3) in vitro in proximity to and within the oxygen-dependent degradation domain (ODDD). SUMO conjugation is promoted in vitro by the E3 SUMO ligase RanBP2/Nup538 and SUMO modification in vivo does not change HIF-1 alpha turnover rate. Using cotransfection of siRNA targeted to endogenous HIF-1a together with HIF-1 alpha siRNA-resistant expression vectors carrying mutations for SUMO modification we demonstrate increased hypoxia- response element-dependent transcriptional
activity for SUMO-deficient HIF-1 alpha. These results indicate that when HIF-1 alpha is conjugated to SUMO its transcriptional activity is decreased and that this is not mediated by a change in the protein's half-life. (c) 2007 Elsevier Inc. All rights reserved.
7.学位论文卢星榕MDM2、p53和SUMO-1影响肝癌细胞凋亡的机理研究2005
第一部分:原发性肝癌MDM2基因表达与p53基因突变及肿瘤侵袭性的关系
目的:以原发性肝癌中MDM2基因表达为指标，探讨其与p53基因突变和肿瘤侵袭性有关的分子机理。
方法:应用RT-PCR方法，总结本院72例原发性肝癌和65例相应癌旁肝组织中MDM2的基因表达，研究其与p53基因突变和肿瘤侵袭性之间的关系。
结果:肝癌组织中MDM2基因表达值(50.17±5.23)％明显高于癌旁肝组织(27.69±7.42)％(P＜0.01)，侵袭性肝癌(59.08±7.27)％明显高于非侵袭性肝癌(37.86±6.36)％(P＜0.05)。侵袭性肝癌的p53基因突变率(72.72％)明显高于非侵袭性肝癌(25.64％)(P＜0.05)。而在不同大小肝癌中，MDM2基因表达值及p53突变率差异无显著意义。无p53基因突变肝癌中的MDM2基因表达值(62.15±8.41)％明显高于有突变者(38.57±4.82)％(P＜0.05)，MDM2低表达组肝癌的p53突变率(56.14％)明显高于MDM2高表达组(13.33％)(P＜0.05)。
结论:MDM2基因过表达、p53基因突变与肝细胞癌的侵袭性有关。MDM2基因过表达可能是p53基因失活的重要机制。
第二部分:原发性肝癌中MDM2、p53蛋白的表达及其临床病理意义
目的:探讨p53、MDM2蛋白表达在原发性肝癌中的相互关系和病理意义。
方法:应用免疫组化方法，总结本院72例原发性肝细胞癌和65例相应癌旁肝组织中p53、MDM2的蛋白表达情况，并联系临床病理结果进行统计学分析。
结果:原发性肝细胞癌中p53、MDM2蛋白表达阳性率癌组织均明显高于癌旁肝组织(分别为
52.78％vs7.69％，P＜0.0001；26.39％vs6.15％，P＜0.01)，p53、MDM2两者间蛋白表达阳性率差异无显著意义(P＞0.05)，MDM2蛋白表达阳性率与肿瘤包膜是否完整及有无血管瘤栓显著相关(分别为P＜0.0001，P=0.0001)，而与肿瘤大小、有无并发肝炎肝硬化及病理分级无关(P＞0.05)。
结论:MDM2、p53蛋白高表达在HCC的发生中起重要作用，MDM2蛋白表达与肝癌侵袭性密切相关。
第三部分:SUMO-1在p53-MDM2反馈调节环中的作用机理
目的:研究小分子泛素样修饰蛋白-1(smallubiquitin-likemodifier-1，SUMO-1)在p53-MDM2反馈调节环中的作用机理。
方法:用含人野生型p53基因质粒pcDNA3-wtp53(pwtp53)、含人双微粒体基因2(murinedoubleminutegene2，MDM2，鼠双微粒体基因2，人同源基因为HDM2)质粒pCMV-HDM1B(pMDM2)、含人SUMO-1基因质粒pcDNA3-His6-SUMO-1(pSUMO-1)和空质粒pcDNA3转染HepG2细胞，获得各转染细胞系，应用Westernblot检测转染后细胞中质粒蛋白的表达及流式细胞技术检测细胞凋亡比例。
结果:转染pwtp53和pMDM2质粒的HepG2细胞均可见p53及MDM2蛋白条带，同时转染pSUMO-1质粒的细胞分别可见被SUMO-1修饰的相对分子量较大的
p53和MDM2蛋白条带，在未转染任何质粒、仅转染空质粒和pSUMO-1质粒的细胞中只检测到少量p53蛋白表达。转染pwtp53及pwtp53+pSUMO-1质粒的
HepG2细胞凋亡比例分别为(16.79±1.62)％和(18.15±1.36)％，转染pwtp53+pMDM2质粒的细胞凋亡比例则下降至(5.17±1.23)％，而转染
pwtp53+pMDM2+pSUMO-1质粒的细胞凋亡比例则上升至(14.06±1.84)％，与转染pwtp53+pMDM2质粒的细胞相比差异有显著性意义(P＜0.01)，其他细胞中的凋亡比例均≤2％，差异无显著性意义(P＞0.05)。
结论:SUMO-1通过与p53蛋白的结合或翻译后修饰，抑制MDM2等癌基因蛋白对p53蛋白的降解，可增强p53抑癌基因诱导的细胞凋亡。
第四部分:p53、MDM2和SUMO-1在抗肿瘤药物诱导细胞凋亡中的作用机理
目的:探讨p53、MDM2和SUMO-1在化疗药5-Fu诱导的HepG2细胞凋亡中的影响及其作用机理。
方法:5-Fu诱导HepG2细胞产生凋亡，以质粒pCMV-HDM1B(pMDM2)和pcDNA3-His6-SUMO-1(pSUMO-1)转染细胞，应用Westernblot检测经药物诱导及转染前后细胞中内源性p53蛋白的表达强度，流式细胞仪检测细胞凋亡比例变化，免疫荧光显微镜观察p53蛋白在细胞浆及细胞核中的表达。
结果:随药物诱导浓度的增加，HepG2细胞内源性p53蛋白表达强度和细胞凋亡率与对照组相比明显增高(P＜0.01)，于1×10-3mol/L浓度处最强，呈浓度依赖性，细胞浆、细胞核内均可见p53蛋白，且以细胞浆表达为主。转染pMDM2的细胞具有明显的抗凋亡特性，与同浓度未转染细胞相比，p53蛋白表达强度和细胞凋亡率均明显下降(P＜0.01)，p53蛋白表达在细胞浆、细胞核内均减少。共转染pSUMO-1的细胞其浓度-蛋白表达强度-凋亡率曲线又接近未转染细胞，与单纯转染pMDM2细胞相比差异有显著性(P＜0.01)，细胞浆、细胞核内p53蛋白表达重新出现，且以核内更明显。只转染pSUMO-1的细胞p53蛋白在细胞浆、细胞核内的表达和凋亡率与未转染细胞相似，两者间差异无显著性。
结论:SUMO-1通过抑制MDM2对p53在胞浆的降解及增强p53在细胞核内的表达,可促进化疗药物诱导的细胞凋亡率，提高肿瘤细胞对化疗药物的敏感性，在药物诱导的细胞凋亡中具有显著协同效应。
8.OA论文Rodriguez. M S.Desterro. J https://www.doczj.com/doc/3a14742143.html,in. S.Midgley. C https://www.doczj.com/doc/3a14742143.html,ne. D P.Hay. R T SUMO-1 modification
activates the transcriptional response of p53.
The p53 tumour suppressor protein is regulated by ubiquitin-mediated proteasomal degradation. In normal cells p53 is
constitutively ubiquitylated by the Mdm2 ubiquitin ligase. When the p53 response is activated by stress signals p53 levels rise due to inhibition of this degradative pathway. Here we show that p53 is modified by the small ubiquitin-like protein SUMO-1 at a single site, K386, in the C-terminus of the protein. Modification in vitro requires only SUMO-1, the SUMO-1 activating enzyme and ubc9. SUMO-1 and ubiquitin modification do not compete for the same lysine acceptor sites in p53. Overexpression of SUMO-1 activates the transcriptional activity of wild-type p53, but not K386R p53 where the SUMO-1 acceptor site has been mutated. The SUMO-1 modification pathway therefore acts as a potential regulator of the p53 response and may represent a novel target for the development of therapeutically useful modulators of the p53 response.
9.外文期刊Okubo S.Hara F.Tsuchida Y.Shimotakahara S.Suzuki S.Hatanaka H.Yokoyama S.Tanaka H.Yasuda
H.Shindo H NMR structure of the N-terminal domain of SUMO ligase PIAS1 and its interaction with
tumor suppressor p53 and A/T-rich DNA oligomers.
A member of the PIAS (protein inhibitor of activated STAT) family of proteins, PIAS1, have been reported to serve as an E3-type SUMO ligase for tumor suppressor p53 and its own. It also was proposed that the N-terminal domain of PIAS1 interacts with DNA as well as p53. Extensive biochemical studies have been devoted recently to understand sumoylations and its biological implications, whereas the structural aspects of the PIAS family and the mechanism of its interactions with various factors are less well known to date. In this study, the three-dimensional structure of the N-terminal domain (residues 1-65) of SUMO ligase PIAS1 was determined by NMR spectroscopy. The structure revealed a unique four-helix bundle with a topology of an up-down-extended loop-down-up, a part of which the helix-extended loop-helix represented the SAP (SAF-A/B, Acinus, and PIAS) motif. Thus, this N-terminal domain may be referred to as a four-helix SAP domain. The glutathione S-transferase pull-down assay demonstrated that this domain possesses a binding ability to tumor suppressor p53, a target protein for sumoylation by PIAS1, whereas gel mobility assays showed that it has a strong affinity
10.外文期刊Lin JY.Ohshima T.Shimotohno K Association of Ubc9, an E2 ligase for SUMO conjugation,
with p53 is regulated by phosphorylation of p53.
Small ubiquitin-like modifier-1 (SUMO-1) conjugation to the tumor suppressor protein p53 seems to be regulated by murine double minute 2 homologue (Mdm2). It is thought that the physical association of Mdm2 with p53 is important for the enhancement of SUMO-1 conjugation to p53. However, mutant p53 that does not associate with Mdm2 is still sumoylated, albeit at a reduced level, suggesting that sumoylation of p53 is independent of the presence of Mdm2 and there is a direct association of ubiquitin-conjugating enzyme 9 (Ubc9), an E2 ligase for sumoylation, with p53. Here, we report evidence of the direct interaction of Ubc9 with p53. Furthermore, we observed that the interaction of Ubc9 with p53 was regulated by phosphorylation of p53. In particular, in cells treated with adriamycin that is a DNA damaging agent and that enhances phosphorylation of p53 at Ser-20, SUMO conjugation of p53 was severely impaired possibly by reduced affinity of Ubc9 to p53.
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下载时间：2011年1月27日