The rbr-

Supplementary Text
The RBR protein family
Birgit Eisenhaber1,*, Nina Chumak2, Frank Eisenhaber1 and Marie-Theres Hauser2,* 1Research Institute of Molecular Pathology (IMP), Dr. Bohr-Gasse 7, A-1030 Vienna, Austria 2Institute of Applied Genetics and Cell Biology, Department of Plant Science and Plant Biotechnology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, A-1190 Vienna, Austria Email contact: [email protected], [email protected], [email protected], [email protected] *Authors for correspondence Tel. +43-1-79730557, FAX +43-7987153 (Birgit Eisenhaber) Tel. +43-1-36006-6371, FAX +43-36006-6392 (Marie-Theres Hauser) Running Title:
Keywords:
RBR / IBR / E3 ligases / Parkin / PAUL / ARIADNE Abbreviations:
Alternative splicing of RBR proteins
There is yet another level of complexity: Genes of RBR proteins are dispersed throughout the genome. Typically, they contain several exons. Splicing isoforms of RBR-domain containing proteins are widespread. Mladek et al. [1] have studied the Ariadne gene family in Arabidopsis. The 16 AtARI genes are distributed on all five chromosomes at 10 loci. Despite the conserved sequence, they possess distinct gene structures. The number of exons varies between one (AtARI3/CAD52885.1; here and below, the sequence entries of the resulting proteins are listed) and 15 (AtARI5/CAD52887.1, AtARI7/CAD52889.1, and AtARI8/CAD52890.1). The AtARI genes are differentially expressed during plant development and in an organ-specific manner. An alternative splicing event has been experimentally detected for AtARI15 (CAD52897.1). For the human TRIAD3 gene, at least 5 splicing variants have been reported [2]. The two isoforms XAP3 and XAP4 (human Q9BYM8) differ in their N-terminal region. At least for some RBR proteins, alternative splicing appears a mechanism for the control of the subcellular localization and function of the parental RBR protein. For the rat transcription factor RBCK1 (AAC72243.1), another isoform of XAP3, the RBR domain plays a crucial role for its transcriptional activity [3]. RBCK2 (BAA33957.1) has been identified as an alternative splice variant of RBCK1, which lacks the C-terminal part of RBCK1 including the RBR region [3]. Yoshimoto et al. [4] could show that RBCK2 represses the transcriptional activity of RBCK1 by tethering it within the cytoplasm. A similar alternative splice variant lacking the RBR region has Function and Localization
Several human RBR proteins have a function in neurodegenerative and infectious diseases although the molecular mechanisms are not fully understood. Parkin protects dopaminergic neurons from the consequences of mitochondrial damage [6,7] and from harmful levels of aggregation-prone proteins by ubiquitin-mediated proteasomal degradation and/or subcellular tethering [8,9]. In addition, population specific variants of the regulatory region of the Parkin gene act as risk factors for the susceptibility to infections with intracellular pathogenes such as Mycobacterium leprae and Salmonella typhi and Salmonella paratyphi [10-12]. The first evidence that RBR proteins exhibit E3 activity was published for the human HHARI in 1999 (Suppl. Tables 3, 4 and Figure 5) [13]. E3 activity associated with the IBR and the C-RING was also demonstrated for Parkin [14-16] , which catalyzes multiple mono-ubiquitination [17]. As typical E3s, RBR proteins interact with E2s. For most RBR-proteins analyzed so far, the N- RING is essential and functions as recruiting region for specific E2s and substrates (Suppl. Tables 3, 4 and Figure 5). One exception is Parkin where the IBR and the C-RING are responsible for the interaction with E2s, the proteasomal subunit alpha-4, microtubules, SIM2, synphilin-1 and LRRK2. The latter has the tendency to aggregate and enhance the E3 activity of Parkin but is not directly ubiquitinated [18]. Other exceptions are Dorfin and the human Parc protein where interactions have been assigned to either the C- or N-terminal non-RBR part, respectively (Suppl. Thirteen Parkin substrates and 31 interactors have been described so far (Suppl. Tables 3, 4 and Figure 5). The ubiquitination of synphilin-1 is promoted by Parkin. This modification is impaired in all familial-linked mutations of Parkin [19]. Both p38/JTV-1 and FBP-1 localize to the Parkin interactors and chaperones Hsp70 and Hdj-2 and accumulate in Parkin knock out mice and in patients with Parkinson's and Lewy Body disease [20,21]. Dorfin ubiquitinates superoxide dismutase-1 (SOD1) [22] and the Parkin target synphilin-1 [23]. Dorfin reduces the accumulation of mutant SOD1 in mitochondria by enhancing its degradation in the cytosol [24]. The interaction of Parkin through its IBR and N-RING with two regulators of synaptic vesicle dynamics, the septin GTPases, CDCrel-1 and Septin5_v2, promotes their proteasome dependent degradation That Parkin and Dorfin are involved in the ERAD pathway is not only supported by their interaction with ER associated E2s, UBC6 and UBC7 [27]. Parkin also promotes the degradation of un- or mis-folded forms of transmembrane proteins such as Pael-R [28], Synaptotagmin XI [29] and the dopamine transporter (DAT) [30] preventing their accumulation in the ER. Furthermore, Dorfin interacts with the intracellular C-terminus of CaR and with the AAA- ATPase VCP, a proposed component of ERAD [31]. In addition to its single-molecule E3 ligase activity, Parkin was identified as part of the SCF-like E3 complex that includes the F-box/WD repeat protein hSel-10 and Cullin-1. HSel-10 also interacts with cyclin E and Parkin deficiency elevates cyclin E levels causing apoptosis of neuronal cells [28]. Furthermore, Parkin weakly interacts with Rpn10, the regulatory subunit of the 26S proteasome [32]. The C. elegans Parkin homolog PDR-1 is an interactor of the The interaction of HHARI with the proteins 4EHP and SIM2 (which is also a substrate of Parkin) sheds light on the HHARI function [34,35]. Apparently, ubiquitination of 4EHP alters its binding efficiency to the cap of mRNAs, thereby regulating the translational machinery. It is not excluded that 4EHP ubiquitination may be a signal for compartmentalization of specific mRNA populations. The fly and mouse homologues of SIM2 are involved in brain development. SIM2 is poly-ubiquitinated at multiple lysines within the PAS1-PAS2 region (residues 141- 289) but the impact of this modification on transcriptional activity is unknown. The Ariadne member Parc acts as negative regulator of and interacts with the tumor suppressor p53 via its N-terminus [36]. As a sensor of DNA damage and other stresses, p53 must enter the nucleus to deter cell cycle progression and to induce apoptosis. Although Parc was unable to ubiquitinate p53 in vivo and in vitro, its overexpression sequestered p53 into the cytoplasm whereas depletion led to its nuclear relocalization. [36,37]. In the cytoplasm, Parc-bound p53 might be ubiquitinated by additional factors, such as CHIP, a co-chaperone with E4 function [38,39]. The N-terminal region of cullins such as Parc dictates binding to bridging and to substrate specificity proteins. p53 binding to Parc may block these interactions, inactivating a Parc-based, SCF-like E3 ubiquitin ligase. Under stress-free conditions, an active Parc-based complex could form in isolation from nuclear p53. Upon exposure to genotoxic stresses, the stabilization of p53 might allow the cytoplasmic concentration of p53 to rise, acting as an inhibitor of the cytoplasmic Parc complexes [40]. RBR proteins are found in various cellular compartments depending on the characteristics of the additional domains (Figure 4) and the function of their interaction partners. TRIAD1 and HHARI from the Ariadne subfamily are detected predominantly in the nucleus [35,41]. Parkin and PAUL are cytoplasmic [42]. The ARA54-GFP construct is constitutively localized throughout the RBR-proteins can be recruited by their interaction partners to a particular compartment. The example of the nuclear translocation of RBCK1s from the cytoplasm depending on interaction with its RBR-domain deficient splicing variant RBCK2 was discussed in detail above [4]. RBCK1’s transcriptional activity is mediated through the N-RING and IBR domain [44] and can be modulated by the antagonistic action of two other RBCK1 interacting proteins, the positive regulator CBP and its negative regulator PML [45]. For the human XAP3 member, HOIL-1, interaction with hepatitis B virus X protein enhances the ability to activate X-responsive promoters [46]. HOIL-1 ubiquitinates SOCS6 and the oxidized form of the modulator of iron metabolism IRP2 [47,48]. HOIL-1 expression stabilizes SOCS6 by delaying proteasome- mediated protein degradation either by preventing the binding of another protein responsible for SOCS6 degradation or by altering the association to the proteasomal machinery [48]. PAUL redistributes depending on co-expression with its substrate MuSK. The cytoplasmic domain of MuSK is important for the co-localization to MuSK-positive membrane-associated patches [42]. A membrane association of Dorfin, IBRDC1 and RNF144 cannot be excluded in context with their transmembrane helix-like hydrophobic segments (see above). RNF144 was initially identified as transcriptional target p53. Since the abundance of the inhibitor of cyclin- dependent kinase, p21WAF1 correlates with p53RFP expression, it is suggested that p53 induces p53RFP which targets p21WAF1 for degradation driving cells into caspase-independent apoptosis [38,49]. Thus, p53RFP might switch cells from p53-mediated growth arrest to apoptosis [38]. For the two human splicing variants of TRIAD3, ZIN and Triad3A, distinct functions have been assigned. ZIN co-localizes with its substrate RIP in the cytoplasm and regulates apoptosis by repressing RIP induced NF-κB activation [50]. It translocates to the nucleus by co-transfection with the Vif protein of HIV1. Vif is important for viral particle assembly and the stability of the reverse transcription complex [51,52]. Thus, ZIN is an attractive candidate to interfere with HIV replication. The “full length” variant, Triad3A, has an 377 residue extended N-terminus and promotes ubiqutination of the Toll-like receptors, TLR4 and TLR9 [2]. This led to the hypothesis that Triad3A controls the intensity and duration of pro-inflammatory responses mediated by Toll The nuclear-cytoplasmic shuttling is a frequent phenomenon for RBR proteins and is further supported by the protein-interaction map of Drosophila [53]. In this survey, 30, 2, 8, 10, 9 and a single putative interaction partners were identified for ARI-2, ARI-1a, ARI-1b, RNF144, Parkin and PAUL, respectively (Suppl. Table 4). These include cytoplasmic proteins as the ribosomal protein S3, the TNF-receptor associated factor TRAF3, the E3 ligases deltex and Hakai, that promote endocytosis of Notch’s and cadherin, respectively but also β-tubulin. Interestingly, Parkin is anchored to and able to regulate the turnover rate of microtubules and tubulin α-/β- heterodimers by enhancing ubiquitination [29,54,55]. The large protein-protein interaction survey includes also nuclear proteins such as the fly homolog of the homeobox HOX11 protein clawless, the HLH4C transcription factor, the DNA-binding and repressor of Dpp signaling, brinker [56,57] or the evolutionary conserved protein dup that is essential for DNA replication and co-localizes with the origin recognition complex in the nucleus [58]. Furthermore, for the most promiscuous ARI-2 protein, an interaction with a classical shuttling nuclear transport receptor, karyopherin 3, has been detected (Suppl. Table 4) [53]. That Parkin regulates nucleocytoplasmic protein transport and transcription is supported by its interactor and substrate, RanBP2, a component of the nuclear pore complex that associates to the nuclear membrane [59]. RanBP2 belongs to a family SUMO E3 ligases and sumoylates HDAC4. 1. Mladek C, Guger K, Hauser MT: Identification and Characterization of the ARIADNE
Gene Family in Arabidopsis. A Group of Putative E3 Ligases. Plant Physiol 2003,
131:27-40.
2. Chuang TH, Ulevitch RJ: Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like
receptors. Nat Immunol 2004, 5:495-502.
3. Tokunaga C, Kuroda S, Tatematsu K, Nakagawa N, Ono Y, Kikkawa U: Molecular
Cloning and Characterization of a Novel Protein Kinase C-Interacting Protein with
Structural Motifs Related to RBCC Family Proteins.
Biochemical and Biophysical
Research Communications
1998, 244:353-359.
4. Yoshimoto N, Tatematsu K, Koyanagi T, Okajima T, Tanizawa K, Kuroda S: Cytoplasmic
tethering of a RING protein RBCK1 by its splice variant lacking the RING domain.
Biochemical and Biophysical Research Communications 2005, 335:550-557.
5. Kitada T, Asakawa S, Minoshima S, Mizuno Y, Shimizu N: Molecular cloning, gene
expression, and identification of a splicing variant of the mouse parkin gene.
Mammalian Genome 2000, 11:417-421.
6. Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M: Drosophila pink1 is required for mitochondrial function and interacts genetically with
parkin.
Nature 2006, 441:1162-1166.
7. Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J: Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin.
Nature 2006, 441:1157-1161.
8. Cookson MR: THE BIOCHEMISTRY OF PARKINSON'S DISEASE*. Annual Review
of Biochemistry 2005, 74:29-52.
9. Dawson TM, Dawson VL: Molecular Pathways of Neurodegeneration in Parkinson's
Disease. Science 2003, 302:819-822.
10. Ali S, Vollaard AM, Widjaja S, Surjadi C, van de Vosse E, van Dissel JT: PARK2/PACRG polymorphisms and susceptibility to typhoid and paratyphoid fever.
Clinical and Experimental Immunology 2006, 144:425-431.
11. Mira MT, Alcais A, Van Thuc N, Moraes MO, Di Flumeri C, Hong Thai V, Chi Phuong M, Thu Huong N, Ngoc Ba N, Xuan Khoa P, Sarno EN, Alter A, Montpetit A, Moraes ME,
Moraes JR, Dore C, Gallant CJ, Lepage P, Verner A, van de Vosse E, Hudson TJ, Abel L,
Schurr E: Susceptibility to leprosy is associated with PARK2 and PACRG. Nature 2004,
427:636-640.
12. Malhotra D, Darvishi K, Lohra M, Kumar H, Grover C, Sood S, Reddy BSN, Bamezai RNK: Association study of major risk single nucleotide polymorphisms in the common
regulatory region of PARK2 and PACRG genes with leprosy in an Indian population.

Eur J Hum Genet 2005, 14:438-442.
13. Moynihan TP, Ardley HC, Nuber U, Rose SA, Jones PF, Markham AF, Scheffner M, Robinson PA: The Ubiquitin-conjugating Enzymes UbcH7 and UbcH8 Interact with
RING Finger/IBR Motif-containing Domains of HHARI and H7-AP1.
J Biol Chem
1999, 274:30963-30968.
14. Zhang Y, Gao J, Chung KKK, Huang H, Dawson VL, Dawson TM: Parkin functions as
an E2-dependent ubiquitin- protein ligase and promotes the degradation of the
synaptic vesicle-associated protein, CDCrel-1.
PNAS 2000, 97:13354-13359.
15. Shimura H, Hattori N, Kubo Si, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T: Familial Parkinson disease gene product, parkin, is a
ubiquitin-protein ligase.
Nat Genet 2000, 25:302-305.
16. Capili AD, Edghill EL, Wu K, Borden KLB: Structure of the C-terminal RING Finger
from a RING-IBR-RING/TRIAD Motif Reveals a Novel Zinc-binding Domain Distinct
from a RING.
Journal of Molecular Biology 2004, 340:1117-1129.
17. Matsuda N, Kitami T, Suzuki T, Mizuno Y, Hattori N, Tanaka K: Diverse effects of
pathogenic mutations of Parkin that catalyzes multiple monoubiquitylation in vitro. J
Biol Chem
2005,M510393200.
18. Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, West AB, Dawson VL, Dawson TM, Ross CA: Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin and mutant LRRK2
induces neuronal degeneration.
PNAS 2005,0508052102.
19. Chung KKK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM: Parkin ubiquitinates the [alpha]-synuclein-interacting protein, synphilin-
1: implications for Lewy-body formation in Parkinson disease.
Nat Med 2001, 7:1144-
1150.
20. Corti O, Hampe C, Koutnikova H, Darios F, Jacquier S, Prigent A, Robinson JC, Pradier L, Ruberg M, Mirande M, Hirsch E, Rooney T, Fournier A, Brice A: The p38 subunit of the
aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein
biosynthesis and neurodegeneration.
Hum Mol Genet 2003, 12:1427-1437.
21. Ardley HC, Robinson PA: E3 ubiquitin ligases. Essays Biochem 2005, 41:15-30.
22. Niwa Ji, Ishigaki S, Hishikawa N, Yamamoto M, Doyu M, Murata S, Tanaka K, Taniguchi N, Sobue G: Dorfin Ubiquitylates Mutant SOD1 and Prevents Mutant SOD1-mediated
Neurotoxicity.
J Biol Chem 2002, 277:36793-36798.
23. Ito T, Niwa Ji, Hishikawa N, Ishigaki S, Doyu M, Sobue G: Dorfin Localizes to Lewy
Bodies and Ubiquitylates Synphilin-1. J Biol Chem 2003, 278:29106-29114.
24. Takeuchi H, Niwa Ji, Hishikawa N, Ishigaki S, Tanaka F, Doyu M, Sobue G: Dorfin
prevents cell death by reducing mitochondrial localizing mutant superoxide dismutase
1 in a neuronal cell model of familial amyotrophic lateral sclerosis.
Journal of
Neurochemistry
2004, 89:64-72.
25. Choi P, Snyder H, Petrucelli L, Theisler C, Chong M, Zhang Y, Lim K, Chung KKK, Kehoe K, Adamio L: SEPT5_v2 is a parkin-binding protein. Molecular Brain Research
2003, 117:179-189.
26. Hampe C, Ardila-Osorio H, Fournier M, Brice A, Corti O: Biochemical analysis of
Parkinson's disease-causing variants of Parkin, an E3 ubiquitin-protein ligase with
monoubiquitylation capacity.
Hum Mol Genet 2006,ddl131.
27. Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R: An Unfolded Putative
Transmembrane Polypeptide, which Can Lead to Endoplasmic Reticulum Stress, Is a
Substrate of Parkin.
Cell 2001, 105:891-902.
28. Staropoli JF, McDermott C, Martinat C, Schulman B, Demireva E, Abeliovich A: Parkin Is
a Component of an SCF-like Ubiquitin Ligase Complex and Protects Postmitotic
Neurons from Kainate Excitotoxicity.
Neuron 2003, 37:735-749.
29. Huynh DP, Scoles DR, Nguyen D, Pulst SM: The autosomal recessive juvenile Parkinson
disease gene product, parkin, interacts with and ubiquitinates synaptotagmin XI. Hum
Mol Genet
2003, 12:2587-2597.
30. Jiang H, Jiang Q, Feng J: Parkin Increases Dopamine Uptake by Enhancing the Cell
Surface Expression of Dopamine Transporter. J Biol Chem 2004, 279:54380-54386.
31. Ishigaki S, Hishikawa N, Niwa Ji, Iemura Si, Natsume T, Hori S, Kakizuka A, Tanaka K, Sobue G: Physical and Functional Interaction between Dorfin and Valosin-containing
Protein That Are Colocalized in Ubiquitylated Inclusions in Neurodegenerative
Disorders.
J Biol Chem 2004, 279:51376-51385.
32. Sakata E, Yamaguchi Y, Kurimoto E, Kikuchi J, Yokoyama S, Yamada S, Kawahara H, Yokosawa H, Hattori N, Mizuno Y, Tanaka K, Kato K: Parkin binds the Rpn10 subunit
of 26S proteasomes through its ubiquitin-like domain.
EMBO Rep 2003, 4:301-306.
33. Springer W, Hoppe T, Schmidt E, Baumeister R: A Caenorhabditis elegans Parkin
mutant with altered solubility couples {alpha}-synuclein aggregation to proteotoxic
stress.
Hum Mol Genet 2005, 14:3407-3423.
34. Tan NGS, Ardley HC, Scott GB, Rose SA, Markham AF, Robinson PA: Human
homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E
homologous protein, 4EHP.
FEBS Letters 2003, 554:501-504.
35. Okui M, Yamaki A, Takayanagi A, Kudoh J, Shimizu N, Shimizu Y: Transcription factor
single-minded 2 (SIM2) is ubiquitinated by the RING-IBR-RING-type E3 ubiquitin
ligases.
Experimental Cell Research 2005, 309:220-228.
36. Nikolaev AY, Li M, Puskas N, Qin J, Gu W: Parc: A Cytoplasmic Anchor for p53. Cell
2003, 112:29-40.
37. Andrews P, He YJ, Xiong Y: Cytoplasmic localized ubiquitin ligase cullin 7 binds to p53
and promotes cell growth by antagonizing p53 function. Oncogene 2006.
38. Huang J, Xu LG, Liu T, Zhai Z, Shu HB: The p53-inducible E3 ubiquitin ligase p53RFP
induces p53-dependent apoptosis. FEBS Letters 2006, 580:940-947.
39. Anatoly Y.Nikolaev, Wei Gui: PARK A Potential Target for Cancer Therapy. Cell
Cycle 2006, 2:169-171.
40. Skaar JR, Arai T, DeCaprio JA: Dimerization of CUL7 and PARC Is Not Required for
All CUL7 Functions and Mouse Development. Mol Cell Biol 2005, 25:5579-5589.
41. Marteijn JA, van Emst L, Erpelinck-Verschueren CA, Nikoloski G, Menke A, de Witte T, Lowenberg B, Jansen JH, van der Reijden BA: The E3 ubiquitin-protein ligase Triad1
inhibits clonogenic growth of primary myeloid progenitor cells.
Blood 2005,2005-04.
42. Bromann PA, Weiner JA, Apel ED, Lewis RM, Sanes JR: A putative ariadne-like E3
ubiquitin ligase (PAUL) that interacts with the muscle-specific kinase (MuSK). Gene
Expression Patterns
2004, 4:77-84.
43. Ito K, Adachi S, Iwakami R, Yasuda H, Muto Y, Seki N, Okano Y: N-Terminally
extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiquitination of
RING-finger proteins, ARA54 and RNF8.
European Journal of Biochemistry 2001,
268:2725-2732.
44. Tatematsu K, Tokunaga C, Nakagawa N, Tanizawa K, Kuroda S, Kikkawa U: Transcriptional Activity of RBCK1 Protein (RBCC Protein Interacting with PKC 1):
Requirement of RING-Finger and B-Box Motifs and Regulation by Protein Kinases.

Biochemical and Biophysical Research Communications 1998, 247:392-396.
45. Tatematsu K, Yoshimoto N, Koyanagi T, Tokunaga C, Tachibana T, Yoneda Y, Yoshida M, Okajima T, Tanizawa K, Kuroda S: Nuclear-Cytoplasmic Shuttling of a RING-IBR
Protein RBCK1 and Its Functional Interaction with Nuclear Body Proteins.
J Biol
Chem
2005, 280:22937-22944.
46. Cong YS, Yao YL, Yang WM, Kuzhandaivelu N, Seto E: The Hepatitis B Virus X-
associated Protein, XAP3, Is a Protein Kinase C-binding Protein. J Biol Chem 1997,
272:16482-16489.
47. Yamanaka K, Ishikawa H, Megumi Y, Tokunaga F, Kanie M, Rouault TA, Morishima I, Minato N, Ishimori K, Iwai K: Identification of the ubiquitin-protein ligase that
recognizes oxidized IRP2.
Nat Cell Biol 2003, 5:336-340.
48. Bayle J, Lopez S, Iwai K, Dubreuil P, De Sepulveda P: The E3 ubiquitin ligase HOIL-1
induces the polyubiquitination and degradation of SOCS6 associated proteins. FEBS
Letters
2006, 580:2609-2614.
49. Ng Ching-Ching, Arakawa Hirofumi, Fukuda Seisuku, Kondoh Hisato, Nakamura Yusuke: p53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1.
Oncogene 2003, 22:4449-4458.
50. Chen D, Li X, Zhai Z, Shu HB: A Novel Zinc Finger Protein Interacts with Receptor-
interacting Protein (RIP) and Inhibits Tumor Necrosis Factor (TNF)- and IL1-
induced NF-kappa B Activation.
J Biol Chem 2002, 277:15985-15991.
51. Feng F, Davis A, Lake JA, Carr J, Xia W, Burrell C, Li P: Ring Finger Protein ZIN
Interacts with Human Immunodeficiency Virus Type 1 Vif. J Virol 2004, 78:10574-
10581.
52. Lake JA, Carr J, Feng F, Mundy L, Burrell C, Li P: The role of Vif during HIV-1
infection: interaction with novel host cellular factors. Journal of Clinical Virology 2003,
26:143-152.
53. Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao YL, Ooi CE, Godwin B, Vitols E, Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B,
Malcolm R, Varrone Z, Collis A, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F,
Williams J, Neurath K, Ioime N, Agee M, Voss E, Furtak K, Renzulli R, Aanensen N,
Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J, Stanyon CA, Finley RL, Jr.,
White KP, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets RA, McKenna
MP, Chant J, Rothberg JM: A Protein Interaction Map of Drosophila melanogaster.
Science 2003, 302:1727-1736.
54. Yang F, Jiang Q, Zhao J, Ren Y, Sutton MD, Feng J: Parkin Stabilizes Microtubules
through Strong Binding Mediated by Three Independent Domains. J Biol Chem 2005,
280:17154-17162.
55. Ren Y, Zhao J, Feng J: Parkin Binds to alpha /beta Tubulin and Increases their
Ubiquitination and Degradation. J Neurosci 2003, 23:3316-3324.
56. Kirkpatrick H, Johnson K, Laughon A: Repression of Dpp Targets by Binding of Brinker
to Mad Sites. J Biol Chem 2001, 276:18216-18222.
57. Campbell G, Tomlinson A: Transducing the Dpp Morphogen Gradient in the Wing of
Drosophila: Regulation of Dpp Targets by brinker. Cell 1999, 96:553-562.
58. Whittaker AJ, Royzman I, Orr-Weaver TL: Drosophila Double parked: a conserved,
essential replication protein that colocalizes with the origin recognition complex and
links DNA replication with mitosis and the down-regulation of S phase transcripts.

Genes Dev 2000, 14:1765-1776.
59. Um JW, Min DS, Rhim H, Kim J, Paik SR, Chung KC: Parkin Ubiquitinates and
Promotes the Degradation of RanBP2. J Biol Chem 2006, 281:3595-3603.

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