臺灣博碩士論文加值系統

中文摘要

SMT3 (Suppressor of MIF Two 3 protein) 首先是由研究酵母菌(Saccharomyces cerevisiae) 的中心節蛋白 (MIF2) 突變的抑制作用時所分離出的蛋白。因其基因結構類似Ubiquitin故而被稱為Ubiquitin-like protein。除了酵母菌外，在其他高低等真核生物亦發現SMT3的存在。在較低等的真核生物如酵母菌、線蟲、果蠅等僅發現一種SMT3的存在，而在較高等的真核生物如哺乳類則存在三種不同的SMT3 (SMT3A、SMT3B及SMT3C) 。在演化上，這些SMT3蛋白的胺基酸序列具相當強烈的保守性，顯示SMT3在生物體中功能的重要性。目前已知SMT3C為一個修飾作用的蛋白，可與細胞內許多蛋白進行修飾作用如PML、IκBα、P53等，故而掌控細胞內許多的重要生理功能。然而對於SMT3A、SMT3B的功能至今仍不明確，且與SMT3C功能的相關性亦無確切的証實。
為了瞭解SMT3B的功能，我們曾在酵母菌雜交系統中偵測到SMT3B可與Daxx (Fas結合蛋白) C-terminus產生作用。進一步發現三種人類的SMT3 isoforms (3A、3B、3C) 可分別與Daxx N-terminus (Daxx 1)及C-terminus (Daxx 4) 產生結合作用。在Truncated SMT3研究中發現，SMT3與Daxx N-terminus (Daxx 1) 及C-terminus (Daxx 4) 的結合方式並不相同。其中SMT3A、3B較為相似，而異於SMT3C。且在定點突變分析中發現SMT3C與Daxx N-terminus (Daxx 1) 的結合方式是藉由SMT3C C-terminus的 glycine97與Daxx N-terminus (Daxx 1) lysine60產生共價結合，此機制與SMT3C作用在其他目標蛋白經由Ubc9所辨認的SUMO-1一般序列ΨKXE (SUMO-1 consensus sequence) 的共價結合方式相同。此外，在SMT3自我作用 (self-reacting) 的反應中發現，人類的SMT3三個isoforms中僅SMT3C具有自我聚合的現象。
綜合以上結果，我們認為人類SMT3 (SMT3A、3B、3C) 雖然皆可與Daxx產生作用，但結合方式僅SMT3A/B較為相似，而異於SMT3C，但由truncated SMT3實驗顯示SMT3C作用在Daxx N- terminus (Daxx 1) 的方式與SMT3A/B作用在Daxx C-terminus (Daxx 4) 的方式相似，故而推測SMT3A/B似乎亦具有特殊的胺基酸辨認的序列位於Daxx C-terminus部分上。

Abstract

SMT3 (Suppressor of MIF2 3 protein) was identified as a mutation
suppressor in yeast centromere protein MIF2. It is also known as an
ubiquitin-like protein due to the smilarities of their primary structures that
is very conserved during the eukaryotic evolution. Although only one
SMT3 was found in low eukaryotes such as in yeast, three members of
SMT3 (SMT3A, SMT3B and SMT3C) have been identified in high
eukaryotes. It has been known that SMT3C plays an important role in post-translational modification. However, the functions of SMT3A and SMT3B are not well studied yet and the relationship among the SMT3 families remains unclear.
In the present study, Daxx, a Fas binding protein, was demonstrated to bind to SMT3B using yeast two-hybrid assay. It was found that the
N-terminal domain of Daxx (Daxx 1) and the C-terminal domain of Daxx
(Daxx 4), respecifitively, bound to all members of human SMT3
families (including SMT3A, SMT3B and SMT3C). Neverthless,
mechanisms of interactions between the SMT3 families and Daxx
domains remined unclear. Studies on truncated human SMT3 families
have shown that two glycines on the C-terminal end of human SMT3
families were required in the interaction between SMT3 and Daxx
domains, for example, SMT3A and SMT3B required C-terminal two glycines on the Daxx 4 domain where as SMT3C required C-terminal two glycines on the Daxx 1 domain. Morever, truncated SMT3C and Daxx 1 domain point mutations have also indicated that the the linkage of
glycine97 of SMT3C and the lysine60 of Daxx 1, in which the SMT3C/
SUMO-1 consensus sequence ΨKXE was found. Further, SMT3C was
the only member of the SMT3 families capable of self-reacting.
Results also suggested that similar mechanism of interaction
between SMT3A/B and Daxx 1, which is not in accordance with the model proposed in this study regarding the interaction mechanism between SMT3C and Daxx 1. Although two glycines on the C-terminal end of SMT3A/B were necessary for the interactions with Daxx 4 domains, the SMT3C/SUMO-1-consensus sequence ΨKXE was not detected in the Daxx 4 domain. It is therefore, suggested that the mechanism of the interaction between SMT3A/B and Daxx 4 is similar to that of SMT3C and Daxx 1, that may required different binding sequences that is specific for SMT3A/B.

目錄

中文摘要 …………………………………………………… i
英文摘要 …………………………………………………… iii
壹、緒 論
一、SMT3的發現及在酵母菌中的功能 …………………………. 1
二、酵母菌中心節蛋白MIF2與人類中心節蛋白的相關性 ……. 1
三、SMT3在演化上的相關性 ……………………………………. 2
四、SMT3C與Ubiquitin的相關性 ……………………………….. 3
五、SMT3C目前已知的功能 …………………………………….. 5
六、Daxx的發現及功能 ………………………………………...… 8
貳、研究目的 …………………………………………….. 11
參、研究策略及方法
一、研究策略 ……………………………………………..…… 12
二、研究材料及方法
(一)質体的建構 (Plasmid constructions)
1.Primers的設計及合成 ……………………………………… 13
2.聚合酶鏈反應PCR (Polymerase chain reaction) ..………….. 18
3.DNA電泳分析 …………………………………………….…. 20
4.DNA的轉殖 (DNA cloning) …………………………………. 20
(二)大腸桿菌的形質轉換 (E. coli transformation )
1.勝任細胞的製備 (Preparation of competent cells) ………….. 21
2.DH5α形質轉換 (Transformation) ……………..….….…… 22
(三)重組DNA的篩選 (Recombinant DNA selection) ……….…. 22
(四) DNA定序 (DNA sequencing)
1.定序膠片的製作 (Preparation of autosequence gel) ……….. 23
2.DNA定序分析 (DNA sequencing analysis) ……..………… 24
(五)酵母菌二次雜交分析 (Yeast two-hybrid assay)
1.酵母菌勝任細胞的配製 (Preparation of yeast competent cells) 24
2.酵母菌的形質轉換 (Yeast transformation) ………..………. 25
3.β-galactosidease Assay
3.1.Colony-Lift Filter Assay ………………………………. 26
3.2.Liquid Culture Assay …………………….………… 27
肆、結 果 ……………………………………………….. 29
伍、討 論 ……………………………………………………….. 34
陸、參考文獻 ………………………………………….….. 42
柒、圖 表
(一) 圖目錄
圖一、不同生物間的SMT3蛋白的胺基酸序列比較 …….….. 49
圖二、Ubiquitin與SMT3/SUMO的胺基酸序列比較 ……... 50
圖三、Ubiquitin與SUMO-1/SMT3C作用方式的比較 …….. 51
圖四、SUMO-1 作用在Daxx的結合區域 …….…………… 52
圖五、SMT3與Daxx作用可能產生的功能 ……………….... 53
(二) 表目錄
表一、Ubc9辨別Substrates的胺基酸序列 (SUMO-1-CS) ….. 54
表二、目前在酵母菌雜交系統中發現的Daxx作用蛋白 …… 55
表三、酵母菌雜交分析SMT3與Daxx的交互作用 ………… 56
表四、酵母菌雜交分析SMT3A與Daxx的作用區域 …….… 57
表五、酵母菌雜交分析SMT3B與Daxx的作用區域 …….… 58
表六、酵母菌雜交分析SMT3C與Daxx的作用區域 …….… 59
表七、酵母菌雜交分析Truncated SMT3A與Daxx的作用 60
表八、酵母菌雜交分析Truncated SMT3B與Daxx的作用 61
表九、酵母菌雜交分析Truncated SMT3C與Daxx的作用 62
表十、雜交分析Truncated SMT3A與Daxx 1及Daxx 4作用 63
表十一、雜交分析Truncated SMT3B與Daxx 1及Daxx 4作用 64
表十二、雜交分析Truncated SMT3C與Daxx 1及Daxx 4作用 65
表十三、突變分析探討SMT3C與Daxx 1 (Lys60)的作用 66
表十四、酵母菌二次雜交分析SMT3 與Daxx作用的強弱 67
表十五、酵母菌雜交分析探討SMT3與Ubiquitination的相關性68

參考文獻

1.Adams, J. M. and Cory, S. (1998) The Bcl-2 Protein Family: Arbiters
of Cell Survival. Science 281: 236.
2.Ashkenazi, A. and Dixit, V. M. (1998) Death Receptors: Signaling
and Modulation. Science 281: 1305-1308.
3.Arends, M. J., Morris, R. G. and Wyllie, A. H. (1990) The Role of the
Endonuclease. Am. J. Patbol. 136: 593-608.
4.Baker, R. E., Fitzgerald-Hayes, M. and O’Brien, T. C. (1989)
Purification of the Yeast Centromere Binding Protein CP1 and a Iutational Analysis of Its Binding Site. J. Biol. Chem. 264: 10843
-10850.
5. Bayer, P., Arndt, A., Metzger, S., Mahajan, R., Melchior, F., Jaenicke,
R. and Becker, J. (1998) Structure Determination of the SmallUbiqui-tin-related Modifier SUMO-1. J. Mol. Biol. 280: 275-286.
6. Bloom, K. (1993) The Centromere Frontier: Kinetochore Components
, Microtubule-Based Motility, and the CEN-Value Paradox. Cell 73:
621-624.
7. Brown, M. T. (1995) Sequences similarities between the yeast chro-
mosome segregation protein Mif2 and the mammalian centromere
protein CENP-C. Gene 160: 111-116.
8. Brown, M. T., Goetsch, L. and Hartwell, L. H. (1993) MIF2 Is Re-
quired for Mitotic Spindle Integrity during Anaphase Spindle
elongation in Saccharomyces cerevisiae. Cell Biol. 123: 387-403.
9. Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E. and Freemont, P.
S. (1996) PIC 1, a novel ubiquitin-like protein which interacts with
the PML component of a multiprotein complex that is disrupted in
acute promyelocytic leukaemia. Oncogene 13: 971-982.
10. Chelbi-Alix, M. K. and de The H. (1999) Herpes virus induced
proteasome-dependent degradation of the nuclear bodies-associated
PML and Sp100 proteins. Oncogene 18: 935-941.
11.Ciechanover, A. (1994) The Ubiquitin-Proteasome Proteolytic
Pathway. Cell 79: 13-21.
12. Chen, A., Mannen, H. and Li, S. S.-L. (1998) Characterization of
mouse ubiquitin-like SMT3A and SMT3B cDNA and gene/
pseudogenes. Biochem. Mol. Biol. Int. 46: 1161-1174.
13. Desterrro, J. M. P., Rodriguez, M. S., Kemp, G. D. and Hay, R. T.
(1999) Identification of the Enzyme Required for Activation of the
Small Ubiquitin-like Protein SUMO-1. J. Biol. Chem. 274: 10618-10
624.
14. Dohmen, R. J., Stappen, R., McGrath, J. P., Forrova, H., Kolarov, J.,
Goffeau, A. and Varshavsky, A. (1995) An Essential Yeast Gene
Encoding a Homolog of Ubiquitin-activating Enzyme. J. Biol. Chem.
270: 18099-18109.
15. Duprez, E., Saurin, A. J., Desterro, J. M., Lallemand-Breitenbach, V.,
Howe, K., Boddy, M. N., Solomon, E., de The H., Hay, R. T. and
Freemont, P. S. (1999) SUMO-1 modification of acute promyelocytic
leukaemia protein PML: implications for nuclear localisation.J.
Cell Sci. 112:381-393.
16. Epps, J. L. and Tanda, S. (1998) The Drosophila semushi mutation
blocks import of Bicoid during embryogenesis. Curr. Biol. 8:
1277-1280.
17. Everett, R.D., Earnshaw, W.C., Pluta, A.F., Sternsdorf, T., Ainsztein,
A.M., Carmena, M., Ruchaud, S., Hsu, W.-L. and Orr, A. (1999) A
dynamic connection between centromeres and ND10 proteins.
J. Cell Sci. 12: 3443-3454.
18. Evan, G. and Littlewood, T. (1998) A Matter of Life and Cell Death.
Science 281: 1317-1322
19. Gostissa, M., Hengstermann, A., Fogal, V., Sandy, P., Schwarz, S.E.,
Scheffner, M. and Del Sal, G.(1999) Activation of p53 by conjugation
To the ubiquitin-like protein SUMO-1. EMBO J 18: 6462-6471
20. Green, D. R. and Reed, J. C. (1998) Mitochondria and Apoptosis.
Science 281: 1309-1312.
21. Haaf, T., Warburton, P. E. and Willard, H. F. (1992) Integration of
Human α-Satellite DNA into Simian Chromosomes: Centromere Protein Binding and Disruption of Normal Chromosome Segregation. Cell 70 : 681-696.
22. Haas, A. L., Katzung, D. J., Reback, P. M. and Guarino, L. A. (1996)
Functional Characterization of the Ubiquitin Variant Encoded by the
Baculovirus Autographa californica. Biochemistry 35: 5385-5394.
23. Hochstrasser, M. (1996) Ubiquitin-dependent protein degradation.
Annu. Rev. Genet. 30: 405-439.
24. Hllenbach, A.D., Sublett, J.E., McPherson, C.J. and Grosveld, G.
(1999) The Pax3-FKHR oncoprotein is unresponsive to the Pax3-
associated repressor hDaxx. EMBO J. 18: 3702-3711.
25. Howe, K., Williamson, J., Boddy, N., Sheer, D., Freemont, P. and
Solomon, D. (1998) The Ubiquitin-Homology Gene PIC1:
Characterization of Mouse (Pic1) and Human (UBL1) Genes and
Pseudogenes.Genomics 47: 92-100.
26. Hsu, H., shu, H.-B., Pan, M.-G. and Goeddel D. V. (1996) TRADD-
TRAF2 and TRADD-FADD Interactions Define Two Distinct TNF
Receptor 1 Signal Transduction Pathways. Cell 84: 299-308.
27.Huang, H.-W., Tsoi, S. C.-M., Sun, H. and Li, S. S.-L. (1998)
Identification and characterization of the SMT3 cDNA and gene
encoding ubiquitin-like protein from Drosophila Melanogaster.
Biochem. Mol. Biol. Int. 46: 775-785.
28. Ishov, A.M., Sotnikov, A.G., Negorev, D., Vladimirova, O.V., Neff,
N., Kamitani, T., Yeh, E.T.H., Strauss III, J.F. and Maul, G.G. (1999)
PML IS Critical for ND10 Formation and Recruits the PML-
interacting protein Daxx to Nuclear Structure when Modified by
SUMO-1. J. Cell Biol. 147: 221-233.
29.Johnson, E. S., Schwienhorst, I., Dohmen, R. J. and Blobel, G.(1997)
The ubiquitin-like protein Smt3p is activated for conjugation to
Proteins by an Aos1p/Uba2p heterodimer. EMBO J. 16: 5509-5519.
30.Kamitani, T., Nguyen, H. P. and Yeh, E. T. H. (1997) Preferential
Modification of Nuclear Proteins by a Novel Ubiquitin-like Molecule
J. Biol. Chem. 372: 14001-14004.
31.King, R. W., Peters, J.-M., Tugendreich, S., Rolfe, M., Hieter, P. and
Kirschner, M. W. (1995) A 20S Complex Containing CDC27 and CD
C16 Catalyzes the Mitosis-Specific Conjugation of Ubiquitin to
Cyclin B. Cell 81: 279-288.
32.King, R. W., Deshaies, R. J., Peters, J.-M. and Kirschner, M. W. (1996) How Proteolysis Drives the Cell Cycle. Science 274: 1652-1659.
33. Kiriakidou, M., Driscoll, D. A., Lopez-Guisa, J. M. and Strauss, J. F.
(1997) Cloning and Expression of Primate Daxx cDNA and Mapping
of the Human Gene to Chromosome 6p21.3 in the MHC Region.
DNA and Cell Biol. 16: 1289-1298.
34. Kumar, S., Yoshida, Y. and Noda, M. (1993) Cloning of a cDNA
which encodes a novel ubiquitin-like protein. Biochem. Biophys. Res.
Commun. 195: 393-399
35.Lapenta, V., Chiurazzi, P., Spek, P. V. D., Pizzuti, A., Hanaoka, F. and
Brahe, C. (1997) SMT3A, a Human Homologue of the S. cerevisiae
SMT3 Gene, Maps to Chromosome 21qter and Defines a Novel Gene
Family. Genomics 40: 362-366.
36. Lehembre, F., Badenhorst, P., Muller, S., Travers, A., Schweisguth, F.
and Dejean, A. (2000) Covalent Modification of the Transcriptional
Repressor Tramtrack by the Ubiquitin-Related Protein SMT3 in
Drosophila flies. Mol. Cell. Biol. 20: 1072-1082.
37. Li, H., Leo, C., Zhu, J., Wu, X., Oneil, J., Park, E-J. and Chen J.D.
(2000) Sequestration and Inhibition of Daxx-Mediated
Transcriptional Repression by PML. Mol. Cell. Biol. 20: 1748-1796.
38. Li, S.-J. and Hochstrasser, M. (1999) A new protease required for cell
-cycle progression in yeast. Nature 398: 246-251.
39. Liou, M.-L. and Liou, H.-C. (1999) The Ubiquitin-homology Protein,
DAP1, Associates with Tumor Necrosis Factor Receptor (p60) Death
Domain and Induces Apoptosis. J. Biol. Chem. 274: 10145-10153.
40. Liu, Z.-G., Hsu, H., Goeddel, D. V. and Karin, M. (1996) Dissection
of TNF Receptor 1 Effector Functions: JNK Activation Is Not Linked
to Apoptosis While NF-κB Activation Prevents Cell Death. Cell 87:
565-576.
41. Liu, Q., Jin, C., Liao, X., Shen, Z., Chen, D. J. and Chen, Y. (1999)
The Binding Interface between an E2 (UBC9) and a Ubiquitin
Homologue (UBL1). J. Biol. Chem. 274: 16979-16987.
42. Loeb, K. R. and Hass, A. L. (1992) The Interferon-inducible 15-kDa
Homolog Conjugates to Intracellular Proteins. J. Biol. Chem. 267:
7806-7813.
43. Mahajan, R., Gerace, L. and Melchior, F. (1998) Molecular
Characterization of the SUMO-1 Modification of RanGAP1 and Its role in Nuclear Envelope Association. J. Cell Biol. 140: 259-270.
44. Mahajan, R., Delphin, C., Guan, T., Gerace, L. and Melchior, F. (1997
) A Small Ubiquitin-Related Polypeptide Involved in Targeting RanG
AP1 to Nuclear Pore Complex Protein RanBP2. Cell 88: 97-107.
45. Mannen, H., Tseng, H.-M., Cho, C.-L. and Li, S. S.-L. (1996) Cloning
and Expression of Human Homolog HSMT3 to Yeast SMT3
Suppressor of MIF2 Mutations in a Centromere Protein Gene. Biochem. Biophys. Res. Commun. 222: 178-180.
46. Martin, S. J., Green D. R. and Cotter, T. G. (1994) Dicing with death:
dissecting the components of the apoptosis machinery. TIBS 19: 26-30
47. Matunis, M.J., Coutavas, E. and Blobel, G. (1996) A Novel Ubiquitin
-like Modification Modulates the Partitioning of the Ran-GTPase
activating Protein RanGAP1 between the Cytosol and the Nuclear
Pore Complex. J. Cell Biol. 135: 1457-1470.
48. Maul, G.G., Negorev, D., Bell, P. and Ishov, A.M. (2000) Review:
Properties and Assembly Mechanisms of ND10, PML Bodies, or
PODs. J. Struct. Biol. 129: 278-287.
49. Meluh, P. B. and Koshland, D. (1995) Evidence that the MIF2 Gene
of Saccharomyces cerevisiae Encodes a Centromere Protein with
Homology to the Mammalian Centromere Protein CENP-C. Mol. Biol. Cell 6: 793-807.
50. Michaelson, J. S. (2000) The Daxx enigma Apoptosis 5: 217-220.
51. Michaelson, J. S., Bader, D., Kuo, F., Kozak, C. and Ledder, P. (1999)
Loss of Daxx, a promiscuously interacting protein, results
extensive apoptosis in early mouse development. Genes Dev. 13: 1918-1923.
52. Moretta, A. (1997) Molecular Mechanisms in Cell-Mediated
Cytotoxicity. Cell 90: 13-18.
53. Muller, S. and Dejean, A. (1999) Viral Immediate-Early Proteins
Abrogate the Modification by SUMO-1 of PML and Sp100 Proteins,
Correlating with Nuclear Body Disruption. J. Virol. 73:
5137-5143.
54.Muller, S., Miller, W. H. and Dejean, A. (1998) Trivalent
Antimonials Induce Degradation of the PML-RARα Oncoprotein and
Reorganization of the Promyelocytic Leukemia Nuclear Bodies in
Acute Promyelocytic Leukemia NB4 Cells. Blood 92: 4308-4316.
55.Nagata, S. (1997) Apoptosis by Death Factor. Cell 88: 355-365.
56. Okura, T., Gong, L., Kamitani, T., Wada, T., Okura, L., Wei, C.-F.,
Chang, H.-M. and Yeh, E. T. H. (1996) Protection Against Fas/APO-1and Tumor Necrosis Factor-Mediated Cell Death by a Novel Protein, Sentrin. J. Immunol. 157: 4277-4281.
57. Pluta, A. F., Earnshaw, W. C. and Goldberg, I. G. (1998)
Interphasespecific association of intrinsic centromere protein CENP-C with HDaxx a death domain-binding protein implicated in Fas-mediated cell death. J. Cell Sci. 111: 2029-2041.
58. Pluta, A. F., Mackay, A. M., Ainsztein, A. M., Goldberg, I. G. and
Earnshaw, W. C. (1995) The Centromere: Hub of Chromosomal
Activities. Scinece 270: 1591-1594.
59. Poukka, H., Aarnisalo, P., Karvonen, U., Palvimo, J. J. and Janne, O.
A.(1999) Ubc9 Interacts with the Androgen Receptor and Activates
Receptor-dependent Transcription. J. Biol. Chem. 274: 19441-19446.
60. Rodriguez, M.S., Desterro, J. M., Lain, S., Midgley, C. A., Lane, D.P.
and Hay, R.T.(1999) SUMO-1 modification activates the
transcriptional response of p53. EMBO J 18: 6455-61
61.Ryu, S.W., Chae, S.K. and Kim, E. (2000) Interaction of Daxx , a Fas
binding protein, with sentrin and Ubc9. Biochem. Biophys. Res.
Commun. 297(1) : 6-10.
62.Saitoth, H. and Hinchey, J. (2000) Functional Heterogeneity of Small
Ubiquitin-related Protein Modifier SUMO-1 versus SUMO-2/3.
J. Biol. Chem. 275: 6252-6258.
63. Saitoth, H., Tomkiel, J., Cooke, C. A., Ratrie, H., Maurer, M.,
Rothfield, N. F. and Earnshaw, W. C. (1992) CENP-C, an
Autoantigen in Scleroderma, Is a Component of the Human Inner Kinetochore Plate. Cell 70: 115-125.
64. Saitoth, H., Pu, R., Cavenagh, M. and Dasso, M. (1997) RanBP2
associates with Ubc9p and a modified form of RanGAP1. Cell
Biol. 94: 3736-3741.
65. Saitoth, H., Sparrow, D. B., Shiomi, T., Pu, R. T., Nishimoto, T.,
Mohun, T. J. and Dasso, M. (1997) Ubc9p and the conjugation of
SUMO-1 to RanBP2. Curr. Biol. 8: 121-124.
66. Sampsom, D.A., Wang M. and Matunis, M. J. (2001) The SUMO-1
consensus sequence mediates Ubc9 binding is essential for SUMO-1
modification. J. Biol. Chem. 276: 21664-9
67.Schwienhorst., Johnson, E.S. and Dohmen, R.J. (2000) SUMO
conjugation and deconjugation. Mol. Gen. Genet. 263: 771-786.
68. Shen, Z., Pardington-Purtymun, P. E., Comeaux, J. C., Moyzis, R. K.
and Chen, D. J. (1996) Associations of UBE2I with RAD52, UBL1,
p53 and RAD51 Proteins in a Yeast Two-Hybrid System. Genomics
37: 183-186.
69. Shen, Z., Pardington-Purtymun, P. E., Comeaux, J. C., Moyzis, R. K.
and Chen, D. J. (1996) UBL1, a human ubiquitin-like protein
associating with human RAD51/RAD52 proteins. Genomics 36:
271-279.
70.Sternsdorf, T., Jensen, K., Reich, B. and Will, H. (1999) The Nuclear
Dot Protein Sp100, Characterization of Domains Necessary for
Dimerization, Subcellular Localization and Modification by Small Ubiquitin-like Modifiers. J. Biol. Chem. 274: 12555-12566.
71. Takahashi, Y., Iwase, M., Konishi, M., Tanaka, M., Toh-e, A. and
Kikuchi, Y. (1999) SMT3, a SUMO-1 Homolog, Is Conjugated to Cdc3, a Component of Septin Rings at the Mother-Bud Neck in Budding Yeast. Biochem. Biophys. Res. Commun. 259: 582-587.
72.Thornberry, N. A. and Lazebnik, Y. (1998) Caspases: Enemies Within Science 281: 1312-1316.
73.Torii, S., Egan, D.A., Evans, R.A.and Reed, J.C. (1999) Human Daxx
regulates Fas-induced apoptosis form nuclear PML oncogenic
domain(PODs). EMBO J. 18: 6037-6049.
74.Wyllie, A. H. (1980) Glucocorticoid-induced thymocyte apoptosis is
associated with endogenous endonuclease activation. Nature 284: 555-556.
75.Yang, X., Khosravi-Far, R., Chang, H. Y. and Baltimore, D. (1997)
Daxx, a Novel Fas-Binding Protein That Activates JNK and
Apoptosis. Cell 89: 1067-1076.
76.Yokoyama, N., Hayashi, N., Seki, T., Pante, N., Ohba, T., Nishii, K.,
Kuma, K., Hayashida, T., Miyata, Y., Aebi, U., Fukui, M. and
Nishimoto, T. (1995) A giant nucleopore protein that binds Ran/TC4.
Nature 376: 184-188.
77.Zhong, B.S., Salomoni, P., Ronchetti, S., Guo, A., Ruggero, D. and
Pandolfi, P.P.(2000) Promyelocytic Leukemia Protein (PML) and
Daxx Participate in a Novel Nuclear Pathway for Apoptosis. J. Exp.
Med. 191: 631-639.