Journal Mobile Options
Table of Contents
Vol. 19, No. 3, 2011
Issue release date: August 2011
Section title: Original Paper
Neurosignals 2011;19:128–141
(DOI:10.1159/000327819)

Targeted Deletion of CASK-Interacting Nucleosome Assembly Protein Causes Higher Locomotor and Exploratory Activities

Chung W.-C.a, b · Huang T.-N.b · Hsueh Y.-P.a, b
aGraduate Institute of Life Sciences, National Defense Medical Center, and bInstitute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC
email Corresponding Author

Abstract

CASK-interacting nucleosome assembly protein (CINAP) has been shown to interact with the calcium/calmodulin-dependent serine kinase (CASK) and the T-box transcription factor T-brain-1 (Tbr1) thus modulating the expression of N-methyl-D-aspartic acid receptor subunit 2b (NMDAR2b) in cultured hippocampal neurons. To explore the physiological significance of CINAP in vivo, CINAP knockout mice were generated and subjected to biochemical, anatomical, and behavioral analyses. Unexpectedly, CINAP deletion did not impact NMDAR2b expression, and these CINAP knockout mice were consistently comparable to wild-type littermates in terms of immediate memory (assessed with the Y maze) and associative memory (evaluated by conditioned taste aversion and contextual and auditory fear conditioning). Although CINAP deletion did not obviously influence learning and memory behaviors, CINAP knockout mice exhibited higher locomotor and exploratory activities. Compared with wild-type littermates, the horizontal and vertical movements of the CINAP knockout mice were higher in a novel environment; in home cages, rearing, sniffing, and jumping also occurred more frequently in CINAP knockout mice. These observations suggest that although CINAP deletion in mice does not influence learning and memory behaviors, CINAP is required for restriction of locomotor and exploratory activities.

© 2011 S. Karger AG, Basel


  

Key Words

  • Cognitive impairment
  • Exploration
  • Locomotion
  • N-methyl-D-aspartic acid receptor subunit 2b
  • Nucleosome assembly protein

References

  1. Hackett A, Tarpey PS, Licata A, Cox J, Whibley A, Boyle J, Rogers C, Grigg J, Partington M, Stevenson RE, Tolmie J, Yates JR, Turner G, Wilson M, Futreal AP, Corbett M, Shaw M, Gecz J, Raymond FL, Stratton MR, Schwartz CE, Abidi FE: CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes. Eur J Hum Genet 2010;18:544–552.
  2. Tarpey PS, Smith R, Pleasance E, et al: A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet 2009;41:535–543.
  3. Piluso G, D’Amico F, Saccone V, Bismuto E, Rotundo IL, Di Domenico M, Aurino S, Schwartz CE, Neri G, Nigro V: A missense mutation in CASK causes FG syndrome in an Italian family. Am J Hum Genet 2009;84:162–177.
  4. Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov VV, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LR, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K: Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet 2008;40:1065–1067.
  5. Atasoy D, Schoch S, Ho A, Nadasy KA, Liu X, Zhang W, Mukherjee K, Nosyreva ED, Fernandez-Chacon R, Missler M, Kavalali ET, Sudhof TC: Deletion of CASK in mice is lethal and impairs synaptic function. Proc Natl Acad Sci USA 2007;104:2525–2530.
  6. Hsueh YP: Calcium/calmodulin-dependent serine protein kinase and mental retardation. Ann Neurol 2009;66:438–443.
  7. Hsueh YP: The role of the MAGUK protein CASK in neural development and synaptic function. Curr Med Chem 2006;13:1915–1927.
  8. Hsueh YP, Wang TF, Yang FC, Sheng M: Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/lin-2. Nature 2000;404:298–302.
  9. Wang GS, Hong CJ, Yen TY, Huang HY, Ou Y, Huang TN, Jung WG, Kuo TY, Sheng M, Wang TF, Hsueh YP: Transcriptional modification by a CASK-interacting nucleosome assembly protein. Neuron 2004;42:113–128.
  10. Kuo TY, Hong CJ, Chien HL, Hsueh YP: X-linked mental retardation gene CASK interacts with Bcl11A/CTIP1 and regulates axon branching and outgrowth. J Neurosci Res 2010;88:2364–2373.
  11. Ozbun LL, You L, Kiang S, Angdisen J, Martinez A, Jakowlew SB: Identification of differentially expressed nucleolar TGF-beta1 target (DENTT) in human lung cancer cells that is a new member of the TSPY/SET/NAP-1 superfamily. Genomics 2001;73:179–193.
  12. Chai Z, Sarcevic B, Mawson A, Toh BH: Set-related cell division autoantigen-1 (CDA1) arrests cell growth. J Biol Chem 2001;276:33665–33674.
  13. Wang TF, Ding CN, Wang GS, Luo SC, Lin YL, Ruan Y, Hevner R, Rubenstein JL, Hsueh YP: Identification of TBR-1/CASK complex target genes in neurons. J Neurochem 2004;91:1483–1492.
  14. Liu P, Jenkins NA, Copeland NG: A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res 2003;13:476–484.
  15. Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, Alt FW, Westphal H: Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci USA 1996;93:5860–5865.
  16. Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, Ayala R, Stewart AF, Dymecki SM: High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 2000;25:139–140.
  17. Lin CW, Huang TN, Wang GS, Kuo TY, Yen TY, Hsueh YP: Neural activity- and development-dependent expression and distribution of CASK interacting nucleosome assembly protein in mouse brain. J Comp Neurol 2006;494:606–619.
  18. Williams K, Russell SL, Shen YM, Molinoff PB: Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. Neuron 1993;10:267–278.
  19. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH: Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994;12:529–540.
  20. Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY: Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 1994;368:144–147.
  21. Steele AD, Jackson WS, King OD, Lindquist S: The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington’s and prion diseases. Proc Natl Acad Sci USA 2007;104:1983–1988.
  22. Annunziata I, Lanzara C, Conte I, Zullo A, Ventruto V, Rinaldi MM, D’Urso M, Casari G, Ciccodicola A, Miano MG: Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation. Am J Med Genet A 2003;118A:217–222.
  23. Park YJ, Luger K: Structure and function of nucleosome assembly proteins. Biochem Cell Biol 2006;84:549–558.
  24. Eitoku M, Sato L, Senda T, Horikoshi M: Histone chaperones: 30 years from isolation to elucidation of the mechanisms of nucleosome assembly and disassembly. Cell Mol Life Sci 2008;65:414–444.
  25. Huang TN, Hsueh YP: CASK point mutation regulates protein-protein interactions and Nr2b promoter activity. Biochem Biophys Res Commun 2009;382:219–222.
  26. Huang TN, Chang HP, Hsueh YP: CASK phosphorylation by PKA regulates the protein-protein interactions of CASK and expression of the NMDAR2b gene. J Neurochem 2010;112:1562–1573.
  27. Mignogna P, Viggiano D: Brain distribution of genes related to changes in locomotor activity. Physiol Behav 2010;99:618–626.
  28. Lukaszewska I, Korczynski R, Markowska A, Kostarczyk E: Emotionality and exploratory behavior following cortico-basomedial amygdala lesion in rat. Acta Neurobiol Exp (Wars) 1980;40:911–932.
  29. Hashimoto H, Shintani N, Tanaka K, Mori W, Hirose M, Matsuda T, Sakaue M, Miyazaki J, Niwa H, Tashiro F, Yamamoto K, Koga K, Tomimoto S, Kunugi A, Suetake S, Baba A: Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). Proc Natl Acad Sci USA 2001;98:13355–13360.
  30. Norrholm SD, Das M, Legradi G: Behavioral effects of local microinfusion of pituitary adenylate cyclase activating polypeptide (PACAP) into the paraventricular nucleus of the hypothalamus (PVN). Regul Pept 2005;128:33–41.
  31. Li Q, Holmes A, Ma L, Van de Kar LD, Garcia F, Murphy DL: Medial hypothalamic 5-hydroxytryptamine (5-HT)1a receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1a sequences. J Neurosci 2004;24:10868–10877.
  32. Swanson LW: Cerebral hemisphere regulation of motivated behavior. Brain Res 2000;886:113–164.
  33. Aizawa H, Sato Y, Maekawa M, Fujisawa H, Hirata T, Yuasa S: Development of the amygdalohypothalamic projection in the mouse embryonic forebrain. Anat Embryol (Berl) 2004;208:249–264.
  34. Kandalaft LE, Zudaire E, Portal-Nunez S, Cuttitta F, Jakowlew SB: Differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) exhibits an inhibitory role on tumorigenesis. Carcinogenesis 2008;29:1282–1289.
  35. Pham Y, Tu Y, Wu T, Allen TJ, Calkin AC, Watson AM, Li J, Jandeleit-Dahm KA, Toh BH, Cao Z, Cooper ME, Chai Z: Cell division autoantigen 1 plays a profibrotic role by modulating downstream signalling of TGF-beta in a murine diabetic model of atherosclerosis. Diabetologia 2010;53:170–179.
  36. Tu Y, Wu W, Wu T, Cao Z, Wilkins R, Toh BH, Cooper ME, Chai Z: Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways. J Biol Chem 2007;282:11722–11731.

  

Author Contacts

Dr. Yi-Ping Hsueh
Institute of Molecular Biology, Academia Sinica
128, Academia Rd., Section 2
Taipei 115, Taiwan (ROC)
Tel. +886 2 278 99311, E-Mail yph@gate.sinica.edu.tw

  

Article Information

Received: January 17, 2011
Accepted: March 22, 2011
Published online: May 13, 2011
Number of Print Pages : 14
Number of Figures : 9, Number of Tables : 0, Number of References : 36

  

Publication Details

Neurosignals

Vol. 19, No. 3, Year 2011 (Cover Date: August 2011)

Journal Editor: Ip N.Y. (Hong Kong)
ISSN: 1424-862X (Print), eISSN: 1424-8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

CASK-interacting nucleosome assembly protein (CINAP) has been shown to interact with the calcium/calmodulin-dependent serine kinase (CASK) and the T-box transcription factor T-brain-1 (Tbr1) thus modulating the expression of N-methyl-D-aspartic acid receptor subunit 2b (NMDAR2b) in cultured hippocampal neurons. To explore the physiological significance of CINAP in vivo, CINAP knockout mice were generated and subjected to biochemical, anatomical, and behavioral analyses. Unexpectedly, CINAP deletion did not impact NMDAR2b expression, and these CINAP knockout mice were consistently comparable to wild-type littermates in terms of immediate memory (assessed with the Y maze) and associative memory (evaluated by conditioned taste aversion and contextual and auditory fear conditioning). Although CINAP deletion did not obviously influence learning and memory behaviors, CINAP knockout mice exhibited higher locomotor and exploratory activities. Compared with wild-type littermates, the horizontal and vertical movements of the CINAP knockout mice were higher in a novel environment; in home cages, rearing, sniffing, and jumping also occurred more frequently in CINAP knockout mice. These observations suggest that although CINAP deletion in mice does not influence learning and memory behaviors, CINAP is required for restriction of locomotor and exploratory activities.

© 2011 S. Karger AG, Basel


  

Author Contacts

Dr. Yi-Ping Hsueh
Institute of Molecular Biology, Academia Sinica
128, Academia Rd., Section 2
Taipei 115, Taiwan (ROC)
Tel. +886 2 278 99311, E-Mail yph@gate.sinica.edu.tw

  

Article Information

Received: January 17, 2011
Accepted: March 22, 2011
Published online: May 13, 2011
Number of Print Pages : 14
Number of Figures : 9, Number of Tables : 0, Number of References : 36

  

Publication Details

Neurosignals

Vol. 19, No. 3, Year 2011 (Cover Date: August 2011)

Journal Editor: Ip N.Y. (Hong Kong)
ISSN: 1424-862X (Print), eISSN: 1424-8638 (Online)

For additional information: http://www.karger.com/NSG


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 1/17/2011 7:41:18 AM
Accepted: 3/22/2011
Published online: 5/13/2011
Issue release date: August 2011

Number of Print Pages: 14
Number of Figures: 9
Number of Tables: 0

ISSN: 1424-862X (Print)
eISSN: 1424-8638 (Online)

For additional information: http://www.karger.com/NSG


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Hackett A, Tarpey PS, Licata A, Cox J, Whibley A, Boyle J, Rogers C, Grigg J, Partington M, Stevenson RE, Tolmie J, Yates JR, Turner G, Wilson M, Futreal AP, Corbett M, Shaw M, Gecz J, Raymond FL, Stratton MR, Schwartz CE, Abidi FE: CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes. Eur J Hum Genet 2010;18:544–552.
  2. Tarpey PS, Smith R, Pleasance E, et al: A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. Nat Genet 2009;41:535–543.
  3. Piluso G, D’Amico F, Saccone V, Bismuto E, Rotundo IL, Di Domenico M, Aurino S, Schwartz CE, Neri G, Nigro V: A missense mutation in CASK causes FG syndrome in an Italian family. Am J Hum Genet 2009;84:162–177.
  4. Najm J, Horn D, Wimplinger I, Golden JA, Chizhikov VV, Sudi J, Christian SL, Ullmann R, Kuechler A, Haas CA, Flubacher A, Charnas LR, Uyanik G, Frank U, Klopocki E, Dobyns WB, Kutsche K: Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum. Nat Genet 2008;40:1065–1067.
  5. Atasoy D, Schoch S, Ho A, Nadasy KA, Liu X, Zhang W, Mukherjee K, Nosyreva ED, Fernandez-Chacon R, Missler M, Kavalali ET, Sudhof TC: Deletion of CASK in mice is lethal and impairs synaptic function. Proc Natl Acad Sci USA 2007;104:2525–2530.
  6. Hsueh YP: Calcium/calmodulin-dependent serine protein kinase and mental retardation. Ann Neurol 2009;66:438–443.
  7. Hsueh YP: The role of the MAGUK protein CASK in neural development and synaptic function. Curr Med Chem 2006;13:1915–1927.
  8. Hsueh YP, Wang TF, Yang FC, Sheng M: Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/lin-2. Nature 2000;404:298–302.
  9. Wang GS, Hong CJ, Yen TY, Huang HY, Ou Y, Huang TN, Jung WG, Kuo TY, Sheng M, Wang TF, Hsueh YP: Transcriptional modification by a CASK-interacting nucleosome assembly protein. Neuron 2004;42:113–128.
  10. Kuo TY, Hong CJ, Chien HL, Hsueh YP: X-linked mental retardation gene CASK interacts with Bcl11A/CTIP1 and regulates axon branching and outgrowth. J Neurosci Res 2010;88:2364–2373.
  11. Ozbun LL, You L, Kiang S, Angdisen J, Martinez A, Jakowlew SB: Identification of differentially expressed nucleolar TGF-beta1 target (DENTT) in human lung cancer cells that is a new member of the TSPY/SET/NAP-1 superfamily. Genomics 2001;73:179–193.
  12. Chai Z, Sarcevic B, Mawson A, Toh BH: Set-related cell division autoantigen-1 (CDA1) arrests cell growth. J Biol Chem 2001;276:33665–33674.
  13. Wang TF, Ding CN, Wang GS, Luo SC, Lin YL, Ruan Y, Hevner R, Rubenstein JL, Hsueh YP: Identification of TBR-1/CASK complex target genes in neurons. J Neurochem 2004;91:1483–1492.
  14. Liu P, Jenkins NA, Copeland NG: A highly efficient recombineering-based method for generating conditional knockout mutations. Genome Res 2003;13:476–484.
  15. Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, Alt FW, Westphal H: Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci USA 1996;93:5860–5865.
  16. Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, Ayala R, Stewart AF, Dymecki SM: High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 2000;25:139–140.
  17. Lin CW, Huang TN, Wang GS, Kuo TY, Yen TY, Hsueh YP: Neural activity- and development-dependent expression and distribution of CASK interacting nucleosome assembly protein in mouse brain. J Comp Neurol 2006;494:606–619.
  18. Williams K, Russell SL, Shen YM, Molinoff PB: Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro. Neuron 1993;10:267–278.
  19. Monyer H, Burnashev N, Laurie DJ, Sakmann B, Seeburg PH: Developmental and regional expression in the rat brain and functional properties of four NMDA receptors. Neuron 1994;12:529–540.
  20. Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY: Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Nature 1994;368:144–147.
  21. Steele AD, Jackson WS, King OD, Lindquist S: The power of automated high-resolution behavior analysis revealed by its application to mouse models of Huntington’s and prion diseases. Proc Natl Acad Sci USA 2007;104:1983–1988.
  22. Annunziata I, Lanzara C, Conte I, Zullo A, Ventruto V, Rinaldi MM, D’Urso M, Casari G, Ciccodicola A, Miano MG: Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation. Am J Med Genet A 2003;118A:217–222.
  23. Park YJ, Luger K: Structure and function of nucleosome assembly proteins. Biochem Cell Biol 2006;84:549–558.
  24. Eitoku M, Sato L, Senda T, Horikoshi M: Histone chaperones: 30 years from isolation to elucidation of the mechanisms of nucleosome assembly and disassembly. Cell Mol Life Sci 2008;65:414–444.
  25. Huang TN, Hsueh YP: CASK point mutation regulates protein-protein interactions and Nr2b promoter activity. Biochem Biophys Res Commun 2009;382:219–222.
  26. Huang TN, Chang HP, Hsueh YP: CASK phosphorylation by PKA regulates the protein-protein interactions of CASK and expression of the NMDAR2b gene. J Neurochem 2010;112:1562–1573.
  27. Mignogna P, Viggiano D: Brain distribution of genes related to changes in locomotor activity. Physiol Behav 2010;99:618–626.
  28. Lukaszewska I, Korczynski R, Markowska A, Kostarczyk E: Emotionality and exploratory behavior following cortico-basomedial amygdala lesion in rat. Acta Neurobiol Exp (Wars) 1980;40:911–932.
  29. Hashimoto H, Shintani N, Tanaka K, Mori W, Hirose M, Matsuda T, Sakaue M, Miyazaki J, Niwa H, Tashiro F, Yamamoto K, Koga K, Tomimoto S, Kunugi A, Suetake S, Baba A: Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP). Proc Natl Acad Sci USA 2001;98:13355–13360.
  30. Norrholm SD, Das M, Legradi G: Behavioral effects of local microinfusion of pituitary adenylate cyclase activating polypeptide (PACAP) into the paraventricular nucleus of the hypothalamus (PVN). Regul Pept 2005;128:33–41.
  31. Li Q, Holmes A, Ma L, Van de Kar LD, Garcia F, Murphy DL: Medial hypothalamic 5-hydroxytryptamine (5-HT)1a receptors regulate neuroendocrine responses to stress and exploratory locomotor activity: application of recombinant adenovirus containing 5-HT1a sequences. J Neurosci 2004;24:10868–10877.
  32. Swanson LW: Cerebral hemisphere regulation of motivated behavior. Brain Res 2000;886:113–164.
  33. Aizawa H, Sato Y, Maekawa M, Fujisawa H, Hirata T, Yuasa S: Development of the amygdalohypothalamic projection in the mouse embryonic forebrain. Anat Embryol (Berl) 2004;208:249–264.
  34. Kandalaft LE, Zudaire E, Portal-Nunez S, Cuttitta F, Jakowlew SB: Differentially expressed nucleolar transforming growth factor-beta1 target (DENTT) exhibits an inhibitory role on tumorigenesis. Carcinogenesis 2008;29:1282–1289.
  35. Pham Y, Tu Y, Wu T, Allen TJ, Calkin AC, Watson AM, Li J, Jandeleit-Dahm KA, Toh BH, Cao Z, Cooper ME, Chai Z: Cell division autoantigen 1 plays a profibrotic role by modulating downstream signalling of TGF-beta in a murine diabetic model of atherosclerosis. Diabetologia 2010;53:170–179.
  36. Tu Y, Wu W, Wu T, Cao Z, Wilkins R, Toh BH, Cooper ME, Chai Z: Antiproliferative autoantigen CDA1 transcriptionally up-regulates p21(Waf1/Cip1) by activating p53 and MEK/ERK1/2 MAPK pathways. J Biol Chem 2007;282:11722–11731.