ANALISIS URUTAN NUKLEOTIDA DAN EKSPRESI DARI MUSCLE A-KINASE ANCHORING PROTEIN (mAKAP) MENUNJUKKAN KEMUNGKINAN FUNGSI mAKAP PADA DIFERENSIASI KARDIMIOSIT: PERBANDINGAN EKSPRESI mAKAP PADA JANTUNG MDX DAN KONTROL

Authors

  • Mohammad Saifur Rohman Laboratorium Biokimia FK Unibraw Malang

DOI:

https://doi.org/10.21776/ub.jkb.2004.020.01.1

Abstract

Muscle A-Kinase Anchoring Protein (mAKAP) is an A-kinase anchoring protein (AKAP) which targets cAMP-dependent protein kinase(PKA) to the nuclear envelope. mAKAP not only binds to PKA, but also to the ryanodine receptor (RyR2) and the rolipram-inhibitedcAMP-specific phosphodiesterase (PDE4D3). Amino acid sequence analysis revealed that mAKAP possesses LXCXE andFYDYSYL, the consensus-binding domain of pRB and CBP/p300, respectively. pRB and CBP/p300 are known as a key componentsin cardiomyocyte differentiation processes. Northern blot analysis revealed that mAKAP was expressed in a 13 day old rat heart andits expression increased by 15 days of age when cardiomyocytes reveal a terminal differentiation phenotype. In culturedcardiomyocytes mAKAP was expressed in differentiated but not undifferentiated. Accordingly, mAKAP may play a role in the terminaldifferentiation process through pRB-CBP/p300 functions. Furthermore, we observed mAKAP expression in old mdx heart, a mousemodel of Duchenne muscular dystrophy, compared to control mice. In the control heart, mAKAP transcripts were detected at 6-, 20-,64- and 76-weeks of age. However, mAKAP expression significantly appeared only in 64- and 76-week old mdx hearts. DelayedmAKAP expression in mdx may contribute to impaired function of pRB, CBP/p300, cAMP and Ca2+ complex.Key words: mAKAP, domain architecture, terminal differentiation, pRB, CBP/p300, mdx.

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References

DAFTAR KEPUSTAKAAN

Edwards AS, Scott JD. A-kinase anchoring proteins: protein kinase A and beyond. Curr.Opin.Cell Biol 2000; 12: 217-221.

Colledge M, Scott JD. AKAPs: from structure to function. Trends Cell Biol 1999; 9: 216-221.

Fraser ID, Cong M, Kim J, Rollins EN, Daaka Y, Lefkowitz RJ, Scott JD. Assembly of an A kinase-anchoring protein-beta(2)-adrenergic receptor complex facilitates receptor phosphorylation and signaling. Curr. Biol 2000; 10: 409-412.

Herrgard S, Jambeck P, Taylor SS, Subramaniam S. Domain architecture of a Caenorhabditis elegans AKAP suggests a novel AKAP function. FEBS Lett 2000; 486: 107-111.

Kapiloff MS, Schillace RV, Westphal AM, Scott JD. mAKAP: an A-kinase anchoring protein targeted to the nuclear membrane of differentiated myocytes. J.Cell. Sci 1999; 112: 2725-2736.

Marx SO, Reiken S, Hisamatsu Y, Jayaraman T, Burkhoff D, Rosemblit N, Marks AR. PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor): defective regulation in failing hearts. Cell 2000; 101: 365-376.

Dodge KL, Khouangsathiene S, Kapiloff MS, Mouton R, Hill EV, Houslay MD, Langeberg LK, Scott JD. mAKAP assembles a protein kinase A/PDE4 phosphodiesterase cAMP signaling module. EMBO J 2001; 20: 1921-1930.

Kapiloff MS, Jackson N, Airhart N. mAKAP and the ryanodine receptor are part of a multi-component signaling complex on the cardiomyocyte nuclear envelope. J. Cell. Sci 2001; 114: 3167-3176.

T Ueyama, T Sakoda, S Kawashima, E Hiraoka, K Hirata, H Akita, M Yokoyama. Circ. Res 81 1997; 81: 672-678.

Mochly-Rosen D. Localization of protein kinases by anchoring proteins: a theme in signal transduction. Science 1995; 268: 247-251.

Lee JO, Russo AA, Pavletich NP. Structure of the retinoblastoma tumour-suppressor pocket domain bound to a peptide from HPV E7. Nature 1998; 391: 859-865.

MacLellan WR, Xiao G, Abdellatif M, Schneider MD. A novel Rb- and p300-binding protein inhibits transactivation by MyoD. Mol.Cell. Biol 2000; 20: 8903-8915.

Larose A, Dyson N, Sullivan M, Harlow E, Bastin M. Polyomavirus large T mutants affected in retinoblastoma protein binding are

defective in immortalization. J. Virol 1991; 65: 2308-2313.

Dyson N, Guida P, Munger K, Harlow E. Homologous sequences in adenovirus E1A and human papillomavirus E7 proteins mediate interaction with the same set of cellular proteins. J. Virol 1992; 66: 6893-6902.

Jones RE, Wegrzyn RJ, Patrick DR, Balishin NL, Vuocolo GA, Riemen MW, Defeo-Jones D, Garsky VM, Heimbrook DC, Oliff A. Identification of HPV-16 E7 peptides that are potent antagonists of E7 binding to the retinoblastoma suppressor protein. J. Biol. Chem 1990; 265: 12782-12785.

Taya Y. RB kinases and RB-binding proteins: new points of view. Trends Biochem. Sci 1997; 22: 14-17.

Eckner R, Ewen ME, Newsome D, Gerdes M, DeCaprio JA, Lawrence JB, Livingston DM. Molecular cloning and functional analysis of the adenovirus E1A- associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev 1994; 8: 869-884.

Chrivia JC, Kwok RP, Lamb N, Hagiwara M, Montminy MR, Goodman RH. Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature 1993; 365: 855-859.

Chakraborty S, Senyuk V, Sitailo S, Chi Y, Nucifora G. Interaction of EVI1 with cAMP-responsive element-binding protein- binding protein (CBP) and p300/CBP-associated factor (P/CAF) results in reversible acetylation of EVI1 and in co-localization in nuclear speckles. J. Biol.Chem 2001; 276: 44936-44943.

O'Connor MJ, Zimmermann H, Nielsen S, Bernard HU, Kouzarides T. Characterization of an E1A-CBP interaction defines a novel transcriptional adapter motif (TRAM) in CBP/p300. J. Virol 1999; 73: 3574-3581.

Sartorelli V, Huang J, Hamamori Y, Kedes L. Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C. Mol. Cell. Biol 1997; 17: 1010-1026.

Thorburn J, Carlson M, Mansour SJ, Chien KR, Ahn NG, Thorburn A. Inhibition of a signaling pathway in cardiac muscle cells by active mitogen-activated protein kinase kinase. Mol. Biol.Cell 1995; 6: 1479-1490.

Sugden PH, Clerk A. Cellular mechanisms of cardiac hypertrophy. J. Mol. Med 1998; 76: 725-746.

Claycomb WC. Biochemical aspects of cardiac muscle differentiation. Deoxyribonucleic acid synthesis and nuclear and cytoplasmic deoxyribonucleic acid polymerase activity. J. Biol. Chem 1975; 250: 3229-3235.

Tam SK, Gu W, Mahdavi V, Nadal-Ginard B. Cardiac myocyte terminal differentiation. Potential for cardiac regeneration. Ann. N Y Acad. Sci 1995; 752: 72-79.

Lipinski MM, Jacks T. The retinoblastoma gene family in differentiation and development. Oncogene 1999; 18: 7873-7882.

Sellers WR, Novitch BG, Miyake S, Heith A, Otterson GA, Kaye FJ, Lassar AB, Kaelin WG Jr. Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth. Genes Dev 1998;12: 95-106.

Wiman KG. The retinoblastoma gene: role in cell cycle control and cell differentiation. Faseb J 1993; 7: 841-845.

Chen TT, Wang JY. Establishment of irreversible growth arrest in myogenic differentiation requires the RB LXCXE-binding function. Mol.Cell. Biol 2000; 20: 5571-5580.

Braun T, Bober E, Arnold HH. Inhibition of muscle differentiation by the adenovirus E1a protein: repression of the transcriptional activating function of the HLH protein Myf-5. Genes Dev 1992; 6: 888-902.

Taylor DA, Kraus VB, Schwarz JJ, Olson EN, Kraus WE. E1A-mediated inhibition of myogenesis correlates with a direct physical interaction of E1A12S and basic helix-loop-helix proteins. Mol.Cell. Biol 1993; 13: 4714-4727.

Grana X, Garriga J, Mayol X. Role of the retinoblastoma protein family, pRB, p107 and p130 in the negative control of cell growth. Oncogene 1998; 17: 3365-3383.

Hasegawa K, Meyers MB, Kitsis RN. Transcriptional coactivator p300 stimulates cell type-specific gene expression in cardiac myocytes. J. Biol. Chem 1997; 272: 20049-20054.

Puri PL, Avantaggiati ML, Balsano C, Sang N, Graessmann A, Giordano A, Levrero M. p300 is required for MyoD-dependent cell cycle arrest and muscle- specific gene transcription. EMBO J 1997; 16: 369-383.

Stein RW, Corrigan M, Yaciuk P, Whelan J, Moran E. Analysis of E1A-mediated growth regulation functions: binding of the 300-kilodalton cellular product correlates with E1A enhancer repression function and DNA synthesis-inducing activity. J. Virol 1990; 64:4421-4427.

Miyake S, Sellers WR, Safran M, Li X, Zhao W, Grossman SR, Gan J, DeCaprio JA, Adams PD, Kaelin WG Jr. Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle. Mol. Cell. Biol 2000; 20: 8889-8902.

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2013-04-09

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