- Email: [email protected]
Expression analysis and chromosomal mapping of a novel human gene, APRIL, encoding an acidic protein rich in leucines
Biochimica et Biophysica Acta 1395 Ž1998. 176–180
Short-sequence paper
Expression analysis and chromosomal mapping of a novel human gene, APRIL, encoding an acidic protein rich in leucines Marina Mencinger a,) , Ioannis Panagopoulos a , Juan A. Contreras a ˚ Felix Mitelman a , Pierre Aman
b
a
b
Department of Clinical Genetics, UniÕersity Hospital, S-221 85 Lund, Sweden Department of Cell and Molecular Biology, UniÕersity of Lund, S-221 00 Lund, Sweden Received 4 July 1997; revised 29 August 1997; accepted 1 September 1997
Abstract Clone 120041 was selected from the EST database for sequence similarity to DEK and SET proteins rearranged in leukemias. The ends of the cDNA were isolated by RACE technique. The assembled cDNA encodes an LRR-containing protein of 251 aminoacids designated APRIL Žacidic protein rich in leucines.. APRIL has high similarity to human pp32, also named PHAPI Žbovine I 1PP2A ., and to rat LANP, respectively. APRIL shows tissue-specific expression as shown by Northern blot analysis. It was localized to 15q25 by FISH. q 1998 Elsevier Science B.V. Keywords: APRIL gene; APRIL protein; Gene expression; Chromosomal localization; EST database; Leucine-rich repeat
Fusion genes consisting of one gene encoding an acidic domain and the other a basic DNA-binding domain have been found in a number of solid tumors and leukemias w16x. Acidic regions in transcription factor proteins may act as transactivating domains that interact with other proteins in the transcription complex w7x. The common features of two human oncoproteins DEK and SET are their nuclear localization, and the presence of acidic stretches at the Nand C-terminal, respectively w6x. DEK and SET are
Abbreviations: EST, expressed sequence tags; RACE, rapid amplification of cDNA ends; LRR, leucine-rich repeats; FISH, fluorescence in situ hybridization; cAMP, cyclic adenosine monophosphate ) Corresponding author. Fax: q46 46 131061; E-mail: [email protected]
fused with CAN r nup214 in acute myeloid leukemia and acute undifferentiated leukemia, respectively, carrying tŽ6;9.Žp23;q34. w19,20x. The N-terminal parts of these fusion proteins consist of almost the entire DEK or SET-encoded proteins w19,20x. The purpose of our study was to isolate novel genes encoding acidic regions similar to those in the DEK and SET proteins. These regions were used as queries for the BLAST homology searches w1x against the EST Žexpressed sequence tags. database. Clone 120041 was selected, and sequence-specific primers ŽR788, R768, F750, F985. ŽFig. 1. were designed with anchor primers to perform a 5X and 3X RACE Žrapid amplification of the cDNA ends. w4x. One 5X PCR fragment of 780 bp and two 3X PCR fragments of 430 and 350 bp were amplified. The 780 and 430 bp cDNA fragments were cloned and sequenced. The full length cDNA was assembled by sequences
0167-4781r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved. PII S 0 1 6 7 - 4 7 8 1 Ž 9 7 . 0 0 1 6 5 - 6
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180
177
178
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180
of the 5X end RACE clone, clone 120041, and the 3X end RACE clones, and confirmed by sequences from overlapping clones in the EST database. It has 1371 nucleotides, the initiation codon ATG at position 225, an open reading frame of 251 amino acids, a polyŽ A. signal, and a polyŽA. tail ŽFig. 1ŽA... The amino acid sequence deduced from the cDNA was designated APRIL Ž acidic protein rich in leucines. . During the course of our work M. Vaesen and coworkers deposited to the database two partial cDNA Ž Y07569, Y07570. sequences from the same gene, corresponding to two potentially alternative splicing variants. A YAC human genomic library ŽHGMP resource center. was screened with the 3X end PCR fragment of APRIL w15x. The hybridization signal was identified as YAC 848_b_4. The assignment of APRIL to YAC 848_b_4 was confirmed by PCR amplification Žprimers: F530, R723. ŽFig. 1ŽA.. of the genomic and YAC 848_b_4 derived DNA, which generated identical fragments. PCR products from YAC 848_b_4 DNA, labeled with biotin-dUTP DAPI Ž Boehringer Mannheim., were used for fluorescence in situ hybridization Ž FISH.. Hybridization was specific to 15q25 on metaphase chromosomes Ž Fig. 3.. We searched the Cancer Chromosome Abberation Data Bank w13x for possible involvement of 15q25 as a breakpoint in neoplasia, but no recurrent abnormality with a breakpoint involving this band was found. Deletions of 15q, as determined by loss of heterozygosity studies, have been identified in ovarian carcinomas w3x. A mix of primers ŽR506, R723, R768. Ž Fig. 1Ž A.. was used as a probe for multitissue Northern blots ŽClontech, MTI and MTII. and Northern blots made in our laboratory. Hybridization to a 1.8 kb and a 0.6 kb transcript was seen in skeletal and heart muscles ŽFig. 2. . The larger transcript was present also in the chronic myeloid leukemia cell line K562, and in the Burkitt’s lymphoma cell line, Daudi. No expres-
Fig. 2. Multi-tissue Northern blot hybridized with the mix of primers ŽR506, R723, R768. and actin.
sion was observed in the other 14 tissues examined wdata not shownx. The analysis suggests that the expression of APRIL in nonneoplastic tissues is restricted to the striated muscles. One putative phosphorylation site for cAMP-dependent protein kinase and four sites for casein kinase 2 were identified by PROSITE search in the APRIL protein sequence ŽFig. 1Ž A.. . A nuclear localization is suggested by the presence of three nuclear localization signals Ž Fig. 1Ž A.. w5,8x. The N-terminal part of APRIL contains five putative leucine rich-repeats ŽLRR. ŽFig. 1Ž B... The LRR, each consisting of a short beta-strand and an alpha-helix, adopt a nonglobular horseshoe-shaped form, exposing the inner beta strand layer for protein–protein interactions w9x. The existence of LRR in the APRIL protein is supported by the secondary structure prediction w17x, where alternation of beta-strand and alfa-helix is
Fig. 1. ŽA. The cDNA sequence and the deduced amino acid sequence of the human APRIL gene. The polyŽA. signal is written in bold letters. Putative phosphorylation sites for cAMP-dependent protein kinase and casein kinase 2 are indicated with hatched underline and double hatched underline, respectively. Putative glycosylation sites for asparagine are underlined. The putative nuclear localization signals are indicated with asterisks. Primer positions are marked with arrows. ŽB. Putative LRR in the APRIL protein according to the consensus sequence compiled from all known LRR-containing proteins w9x. Symbols used: ‘.’, any amino acid, ‘-’, gap; ‘?’, amino acid may or may not be present at this position, ‘a’, represents A, V, L, I, F, Y or M. The part of the repeat that is strongly conserved throughout the LRR superfamily is underlined, and the conserved residues are shown in bold. ŽC. Amino acid alignment of APRIL, pp32 and LANP. Identical residues are presented in shadowed boxes. Functionally similar residues are shadowed.
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180
179
We thank Anne-Marie Kolnig and Bodil Strombeck ¨ for technical assistance with FISH. This work was supported by the Swedish Cancer Society, the John and Augusta Persson Foundation for Medical Research, and the Medical Faculty of Lund University.
References
Fig. 3. FISH image showing hybridization at 15q25.
observed. Most of the LRR-containing proteins participate in signal transduction pathways, but functions in cell adhesion, cell development, DNA repair and RNA processing have also been ascribed to them w9x. The APRIL protein has 68% and 65% sequence similarity to the human pp32 and rat LANP, respectively Ž Fig. 1ŽC... The pp32 Žalso named human PHAPI and bovine I 1PP2A . was isolated as a HLA class II binding protein, and was found to inhibit the cytoplasmic serrthr protein phosphatase 2A Ž PP2A. , and the oncogene-induced transformation of rat fibroblasts w2,10,18x. The expression studies of LANP indicate its possible role in differentiation of the cerebellum w12x. Interestingly, the leukemia-associated SET protein Ž also named PHAPII, I PP2A , TAF. , 2 sharing an acidic tail with the APRIL protein, also binds to HLA Class II molecules and inhibits PP2A w11,14,18x. Whether APRIL has similar characteristics as the highly sequence-related proteins remains to be investigated. The tissue-specific expression of APRIL is intriguing. Our observation that APRIL is expressed in two neoplastic cell lines indicates its possible role in neoplasia that needs to be further explored.
w1x S.F. Altschul, W. Gish, W. Miller, E.W. Myers, D.J. Lipman, Basic local alignment search tool, J. Mol. Biol. 215 Ž1990. 403–410. w2x T. Chen, J.R. Brody, F.E. Romantsev, J. Yu, A.E. Kayler, E. Voneiff, F.P. Kuhajda, G.R. Pasternack, Structure of pp32, an acidic nuclear protein which inhibits oncogene-induced transformation foci, Mol. Biol. Cell 7 Ž1996. 2045– 2056. w3x W. Cliby, S. Ritland, L. Hartmann, M. Dodson, K.C. Halling, G. Keeny, K.C. Podratz, R.B. Jenkins, Human epithelial ovarian cancer allelotype, Cancer Res. 53 Ž1993. 2393–2398. w4x C. Coleclough, Use of primer-restriction end adapters in cDNA cloning, Methods Enzymol. 154 Ž1987. 64–83. w5x C. Dingwall, R.A. Laskey, Nuclear targeting sequences – a consensus?, Trends Biochem. Sci. 16 Ž1991. 478–481. w6x M. Fornerod, J. Boer, S. van Baal, M. Jaegle, M. von Lindern, K.G. Murti, D. Davis, J. Bonten, A. Buijs, G. Grosveld, Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements, Oncogene 10 Ž1995. 1739–1748. w7x S. Hahn, Structure Ž?. and function of acidic transcription activators Žcomment., Cell 72 Ž1993. 481–483. w8x D. Kalderon, B.L. Roberts, W.D. Richardson, A.E. Smith, A short amino-acid sequence able to specify nuclear location, Cell 39 Ž1984. 499–509. w9x B. Kobe, J. Deisenhofer, The leucine-rich repeat: a versatile binding motif, Trends Biochem. Sci. 19 Ž1994. 415–421. w10x M. Li, H. Guo, Z. Damuni, Purification and characterization of two potent heat-stable protein inhibitors of protein phosphatase 2A from bovine kidney, Biochemistry 34 Ž1995. 1988–1996. w11x M. Li, A. Makkinje, Z. Damuni, The leukemia associated protein SET is a potent inhibitor of protein phosphatase 2A, J. Biol. Chem. 271 Ž1996. 11059–11062. w12x K. Matsuoka, M. Taoka, N. Satozawa, H. Nakayama, T. Ichimura, N. Takahashi, T. Yamakuni, S.Y. Song, T. Isobe, A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons, Proc. Natl. Acad. Sci. U.S.A. 91 Ž1994. 9670–9674. w13x F. Mitelman, Catalog of Chromosome Aberrations in Cancer, 6th ed., Wiley–Liss, New York, 1997, in press. w14x K. Nagata, H. Kawase, H. Handa, K. Yano, M. Yamasaki, Y. Ishimi, A. Okuda, A. Kikuchi, K. Matsumoto, Replica-
180
w15x
w16x w17x
w18x
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180 tion factor encoded by a putative oncogene, SET, associated with myeloid leukemogenesis, Proc. Natl. Acad. Sci. U.S.A. 92 Ž1995. 4279–4283. D. Pinkel, T. Straume, J.W. Gray, Cytogenetic analysis using quantitative high sensitivity, fluorescence in situ hybridization, Proc. Natl. Acad. Sci. U.S.A. 93 Ž1986. 2934– 2938. T.H. Rabbitts, Chromosomal translocations in human cancer, Nature 372 Ž1994. 143–149. B. Rost, PHD: predicting one-dimensional protein structure by profile-based neural networks, Methods Enzymol. 266 Ž1996. 525–539. M. Vaesen, S. Barnikol Watanabe, H. Gotz, L.A. Awni, T. Cole, B. Zimmermann, H.D. Kratzin, N. Hilschmann, Pu-
rification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII, Biol. Chem. Hoppe Seyler 375 Ž1994. 113–126. w19x M. von Lindern, S. Baal, J. Wiegant, A. Raap, A. Hagemeijer, G. Grosveld, CAN, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of it’s 3X half to different genes: characterization of the SET gene, Mol. Cell. Biol. 12 Ž1992. 3346–3355. w20x M. von Lindern, M. Fornerod, S. Baal, M. Jaegle, T. Wit, A. Buijs, G. Grosveld, The translocation Ž6;9., associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, DEK and CAN, and the expression of a chimeric, leukemia-specific DEK – CAN mRNA, Mol. Cell. Biol. 12 Ž1992. 1687–1697.
Short-sequence paper
Expression analysis and chromosomal mapping of a novel human gene, APRIL, encoding an acidic protein rich in leucines Marina Mencinger a,) , Ioannis Panagopoulos a , Juan A. Contreras a ˚ Felix Mitelman a , Pierre Aman
b
a
b
Department of Clinical Genetics, UniÕersity Hospital, S-221 85 Lund, Sweden Department of Cell and Molecular Biology, UniÕersity of Lund, S-221 00 Lund, Sweden Received 4 July 1997; revised 29 August 1997; accepted 1 September 1997
Abstract Clone 120041 was selected from the EST database for sequence similarity to DEK and SET proteins rearranged in leukemias. The ends of the cDNA were isolated by RACE technique. The assembled cDNA encodes an LRR-containing protein of 251 aminoacids designated APRIL Žacidic protein rich in leucines.. APRIL has high similarity to human pp32, also named PHAPI Žbovine I 1PP2A ., and to rat LANP, respectively. APRIL shows tissue-specific expression as shown by Northern blot analysis. It was localized to 15q25 by FISH. q 1998 Elsevier Science B.V. Keywords: APRIL gene; APRIL protein; Gene expression; Chromosomal localization; EST database; Leucine-rich repeat
Fusion genes consisting of one gene encoding an acidic domain and the other a basic DNA-binding domain have been found in a number of solid tumors and leukemias w16x. Acidic regions in transcription factor proteins may act as transactivating domains that interact with other proteins in the transcription complex w7x. The common features of two human oncoproteins DEK and SET are their nuclear localization, and the presence of acidic stretches at the Nand C-terminal, respectively w6x. DEK and SET are
Abbreviations: EST, expressed sequence tags; RACE, rapid amplification of cDNA ends; LRR, leucine-rich repeats; FISH, fluorescence in situ hybridization; cAMP, cyclic adenosine monophosphate ) Corresponding author. Fax: q46 46 131061; E-mail: [email protected]
fused with CAN r nup214 in acute myeloid leukemia and acute undifferentiated leukemia, respectively, carrying tŽ6;9.Žp23;q34. w19,20x. The N-terminal parts of these fusion proteins consist of almost the entire DEK or SET-encoded proteins w19,20x. The purpose of our study was to isolate novel genes encoding acidic regions similar to those in the DEK and SET proteins. These regions were used as queries for the BLAST homology searches w1x against the EST Žexpressed sequence tags. database. Clone 120041 was selected, and sequence-specific primers ŽR788, R768, F750, F985. ŽFig. 1. were designed with anchor primers to perform a 5X and 3X RACE Žrapid amplification of the cDNA ends. w4x. One 5X PCR fragment of 780 bp and two 3X PCR fragments of 430 and 350 bp were amplified. The 780 and 430 bp cDNA fragments were cloned and sequenced. The full length cDNA was assembled by sequences
0167-4781r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved. PII S 0 1 6 7 - 4 7 8 1 Ž 9 7 . 0 0 1 6 5 - 6
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180
177
178
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180
of the 5X end RACE clone, clone 120041, and the 3X end RACE clones, and confirmed by sequences from overlapping clones in the EST database. It has 1371 nucleotides, the initiation codon ATG at position 225, an open reading frame of 251 amino acids, a polyŽ A. signal, and a polyŽA. tail ŽFig. 1ŽA... The amino acid sequence deduced from the cDNA was designated APRIL Ž acidic protein rich in leucines. . During the course of our work M. Vaesen and coworkers deposited to the database two partial cDNA Ž Y07569, Y07570. sequences from the same gene, corresponding to two potentially alternative splicing variants. A YAC human genomic library ŽHGMP resource center. was screened with the 3X end PCR fragment of APRIL w15x. The hybridization signal was identified as YAC 848_b_4. The assignment of APRIL to YAC 848_b_4 was confirmed by PCR amplification Žprimers: F530, R723. ŽFig. 1ŽA.. of the genomic and YAC 848_b_4 derived DNA, which generated identical fragments. PCR products from YAC 848_b_4 DNA, labeled with biotin-dUTP DAPI Ž Boehringer Mannheim., were used for fluorescence in situ hybridization Ž FISH.. Hybridization was specific to 15q25 on metaphase chromosomes Ž Fig. 3.. We searched the Cancer Chromosome Abberation Data Bank w13x for possible involvement of 15q25 as a breakpoint in neoplasia, but no recurrent abnormality with a breakpoint involving this band was found. Deletions of 15q, as determined by loss of heterozygosity studies, have been identified in ovarian carcinomas w3x. A mix of primers ŽR506, R723, R768. Ž Fig. 1Ž A.. was used as a probe for multitissue Northern blots ŽClontech, MTI and MTII. and Northern blots made in our laboratory. Hybridization to a 1.8 kb and a 0.6 kb transcript was seen in skeletal and heart muscles ŽFig. 2. . The larger transcript was present also in the chronic myeloid leukemia cell line K562, and in the Burkitt’s lymphoma cell line, Daudi. No expres-
Fig. 2. Multi-tissue Northern blot hybridized with the mix of primers ŽR506, R723, R768. and actin.
sion was observed in the other 14 tissues examined wdata not shownx. The analysis suggests that the expression of APRIL in nonneoplastic tissues is restricted to the striated muscles. One putative phosphorylation site for cAMP-dependent protein kinase and four sites for casein kinase 2 were identified by PROSITE search in the APRIL protein sequence ŽFig. 1Ž A.. . A nuclear localization is suggested by the presence of three nuclear localization signals Ž Fig. 1Ž A.. w5,8x. The N-terminal part of APRIL contains five putative leucine rich-repeats ŽLRR. ŽFig. 1Ž B... The LRR, each consisting of a short beta-strand and an alpha-helix, adopt a nonglobular horseshoe-shaped form, exposing the inner beta strand layer for protein–protein interactions w9x. The existence of LRR in the APRIL protein is supported by the secondary structure prediction w17x, where alternation of beta-strand and alfa-helix is
Fig. 1. ŽA. The cDNA sequence and the deduced amino acid sequence of the human APRIL gene. The polyŽA. signal is written in bold letters. Putative phosphorylation sites for cAMP-dependent protein kinase and casein kinase 2 are indicated with hatched underline and double hatched underline, respectively. Putative glycosylation sites for asparagine are underlined. The putative nuclear localization signals are indicated with asterisks. Primer positions are marked with arrows. ŽB. Putative LRR in the APRIL protein according to the consensus sequence compiled from all known LRR-containing proteins w9x. Symbols used: ‘.’, any amino acid, ‘-’, gap; ‘?’, amino acid may or may not be present at this position, ‘a’, represents A, V, L, I, F, Y or M. The part of the repeat that is strongly conserved throughout the LRR superfamily is underlined, and the conserved residues are shown in bold. ŽC. Amino acid alignment of APRIL, pp32 and LANP. Identical residues are presented in shadowed boxes. Functionally similar residues are shadowed.
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180
179
We thank Anne-Marie Kolnig and Bodil Strombeck ¨ for technical assistance with FISH. This work was supported by the Swedish Cancer Society, the John and Augusta Persson Foundation for Medical Research, and the Medical Faculty of Lund University.
References
Fig. 3. FISH image showing hybridization at 15q25.
observed. Most of the LRR-containing proteins participate in signal transduction pathways, but functions in cell adhesion, cell development, DNA repair and RNA processing have also been ascribed to them w9x. The APRIL protein has 68% and 65% sequence similarity to the human pp32 and rat LANP, respectively Ž Fig. 1ŽC... The pp32 Žalso named human PHAPI and bovine I 1PP2A . was isolated as a HLA class II binding protein, and was found to inhibit the cytoplasmic serrthr protein phosphatase 2A Ž PP2A. , and the oncogene-induced transformation of rat fibroblasts w2,10,18x. The expression studies of LANP indicate its possible role in differentiation of the cerebellum w12x. Interestingly, the leukemia-associated SET protein Ž also named PHAPII, I PP2A , TAF. , 2 sharing an acidic tail with the APRIL protein, also binds to HLA Class II molecules and inhibits PP2A w11,14,18x. Whether APRIL has similar characteristics as the highly sequence-related proteins remains to be investigated. The tissue-specific expression of APRIL is intriguing. Our observation that APRIL is expressed in two neoplastic cell lines indicates its possible role in neoplasia that needs to be further explored.
w1x S.F. Altschul, W. Gish, W. Miller, E.W. Myers, D.J. Lipman, Basic local alignment search tool, J. Mol. Biol. 215 Ž1990. 403–410. w2x T. Chen, J.R. Brody, F.E. Romantsev, J. Yu, A.E. Kayler, E. Voneiff, F.P. Kuhajda, G.R. Pasternack, Structure of pp32, an acidic nuclear protein which inhibits oncogene-induced transformation foci, Mol. Biol. Cell 7 Ž1996. 2045– 2056. w3x W. Cliby, S. Ritland, L. Hartmann, M. Dodson, K.C. Halling, G. Keeny, K.C. Podratz, R.B. Jenkins, Human epithelial ovarian cancer allelotype, Cancer Res. 53 Ž1993. 2393–2398. w4x C. Coleclough, Use of primer-restriction end adapters in cDNA cloning, Methods Enzymol. 154 Ž1987. 64–83. w5x C. Dingwall, R.A. Laskey, Nuclear targeting sequences – a consensus?, Trends Biochem. Sci. 16 Ž1991. 478–481. w6x M. Fornerod, J. Boer, S. van Baal, M. Jaegle, M. von Lindern, K.G. Murti, D. Davis, J. Bonten, A. Buijs, G. Grosveld, Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements, Oncogene 10 Ž1995. 1739–1748. w7x S. Hahn, Structure Ž?. and function of acidic transcription activators Žcomment., Cell 72 Ž1993. 481–483. w8x D. Kalderon, B.L. Roberts, W.D. Richardson, A.E. Smith, A short amino-acid sequence able to specify nuclear location, Cell 39 Ž1984. 499–509. w9x B. Kobe, J. Deisenhofer, The leucine-rich repeat: a versatile binding motif, Trends Biochem. Sci. 19 Ž1994. 415–421. w10x M. Li, H. Guo, Z. Damuni, Purification and characterization of two potent heat-stable protein inhibitors of protein phosphatase 2A from bovine kidney, Biochemistry 34 Ž1995. 1988–1996. w11x M. Li, A. Makkinje, Z. Damuni, The leukemia associated protein SET is a potent inhibitor of protein phosphatase 2A, J. Biol. Chem. 271 Ž1996. 11059–11062. w12x K. Matsuoka, M. Taoka, N. Satozawa, H. Nakayama, T. Ichimura, N. Takahashi, T. Yamakuni, S.Y. Song, T. Isobe, A nuclear factor containing the leucine-rich repeats expressed in murine cerebellar neurons, Proc. Natl. Acad. Sci. U.S.A. 91 Ž1994. 9670–9674. w13x F. Mitelman, Catalog of Chromosome Aberrations in Cancer, 6th ed., Wiley–Liss, New York, 1997, in press. w14x K. Nagata, H. Kawase, H. Handa, K. Yano, M. Yamasaki, Y. Ishimi, A. Okuda, A. Kikuchi, K. Matsumoto, Replica-
180
w15x
w16x w17x
w18x
M. Mencinger et al.r Biochimica et Biophysica Acta 1395 (1998) 176–180 tion factor encoded by a putative oncogene, SET, associated with myeloid leukemogenesis, Proc. Natl. Acad. Sci. U.S.A. 92 Ž1995. 4279–4283. D. Pinkel, T. Straume, J.W. Gray, Cytogenetic analysis using quantitative high sensitivity, fluorescence in situ hybridization, Proc. Natl. Acad. Sci. U.S.A. 93 Ž1986. 2934– 2938. T.H. Rabbitts, Chromosomal translocations in human cancer, Nature 372 Ž1994. 143–149. B. Rost, PHD: predicting one-dimensional protein structure by profile-based neural networks, Methods Enzymol. 266 Ž1996. 525–539. M. Vaesen, S. Barnikol Watanabe, H. Gotz, L.A. Awni, T. Cole, B. Zimmermann, H.D. Kratzin, N. Hilschmann, Pu-
rification and characterization of two putative HLA class II associated proteins: PHAPI and PHAPII, Biol. Chem. Hoppe Seyler 375 Ž1994. 113–126. w19x M. von Lindern, S. Baal, J. Wiegant, A. Raap, A. Hagemeijer, G. Grosveld, CAN, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of it’s 3X half to different genes: characterization of the SET gene, Mol. Cell. Biol. 12 Ž1992. 3346–3355. w20x M. von Lindern, M. Fornerod, S. Baal, M. Jaegle, T. Wit, A. Buijs, G. Grosveld, The translocation Ž6;9., associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, DEK and CAN, and the expression of a chimeric, leukemia-specific DEK – CAN mRNA, Mol. Cell. Biol. 12 Ž1992. 1687–1697.