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. 1996 Nov 15;320(Pt 1):253–256. doi: 10.1042/bj3200253

Extracellular high-mobility group 1 protein is essential for murine erythroleukaemia cell differentiation.

B Sparatore 1, M Passalacqua 1, M Patrone 1, E Melloni 1, S Pontremoli 1
PMCID: PMC1217925  PMID: 8947495

Abstract

A high-mobility group 1 (HMG1) protein type isolated from murine erythroleukaemia (MEL) cells promotes acceleration of the differentiation process when added to a MEL cell culture together with the inducer hexamethylene bisacetamide. We now provide direct evidence that the presence of HMG1 protein in the extracellular medium is essential for terminal erythroid differentiation. An extracellular function for HMG1 protein in MEL cell is further supported by a demonstration that this protein is released from MEL cells exposed to the chemical inducer and that the addition of an anti-(HMG1 protein) monoclonal antibody to the cell culture inhibits the differentiation process almost completely. The release of HMG1 protein from MEL cells is modulated by compounds affecting cell calcium homoeostasis, such as a calcium ionophore or verapamil. In fact, in the presence of the ionophore an increased rate of differentiation is accompanied by an enhanced extracellular release of HMG1 protein, whereas in the presence of verapamil both phenomena are significantly decreased.

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Selected References

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  1. Bustin M., Lehn D. A., Landsman D. Structural features of the HMG chromosomal proteins and their genes. Biochim Biophys Acta. 1990 Jul 30;1049(3):231–243. doi: 10.1016/0167-4781(90)90092-g. [DOI] [PubMed] [Google Scholar]
  2. Coffino P., Baumal R., Laskov R., Scharff M. D. Cloning of mouse myeloma cells and detection of rare variants. J Cell Physiol. 1972 Jun;79(3):429–440. doi: 10.1002/jcp.1040790313. [DOI] [PubMed] [Google Scholar]
  3. Corte G., Moretta L., Damiani G., Mingari M. C., Bargellesi A. Surface antigens specifically expressed by activated T cells in humans. Eur J Immunol. 1981 Feb;11(2):162–164. doi: 10.1002/eji.1830110220. [DOI] [PubMed] [Google Scholar]
  4. GREENWOOD F. C., HUNTER W. M., GLOVER J. S. THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963 Oct;89:114–123. doi: 10.1042/bj0890114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goodwin G. H., Johns E. W. Isolation and characterisation of two calf-thymus chromatin non-histone proteins with high contents of acidic and basic amino acids. Eur J Biochem. 1973 Dec 3;40(1):215–219. doi: 10.1111/j.1432-1033.1973.tb03188.x. [DOI] [PubMed] [Google Scholar]
  6. Grosschedl R., Giese K., Pagel J. HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet. 1994 Mar;10(3):94–100. doi: 10.1016/0168-9525(94)90232-1. [DOI] [PubMed] [Google Scholar]
  7. Hardman C. H., Broadhurst R. W., Raine A. R., Grasser K. D., Thomas J. O., Laue E. D. Structure of the A-domain of HMG1 and its interaction with DNA as studied by heteronuclear three- and four-dimensional NMR spectroscopy. Biochemistry. 1995 Dec 26;34(51):16596–16607. doi: 10.1021/bi00051a007. [DOI] [PubMed] [Google Scholar]
  8. Jantzen H. M., Admon A., Bell S. P., Tjian R. Nucleolar transcription factor hUBF contains a DNA-binding motif with homology to HMG proteins. Nature. 1990 Apr 26;344(6269):830–836. doi: 10.1038/344830a0. [DOI] [PubMed] [Google Scholar]
  9. Kane S. A., Lippard S. J. Photoreactivity of platinum(II) in cisplatin-modified DNA affords specific cross-links to HMG domain proteins. Biochemistry. 1996 Feb 20;35(7):2180–2188. doi: 10.1021/bi952240a. [DOI] [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Melloni E., Pontremoli S., Damiani G., Viotti P., Weich N., Rifkind R. A., Marks P. A. Vincristine-resistant erythroleukemia cell line has marked increased sensitivity to hexamethylenebisacetamide-induced differentiation. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3835–3839. doi: 10.1073/pnas.85.11.3835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Melloni E., Sparatore B., Patrone M., Pessino A., Passalacqua M., Pontremoli S. Extracellular release of the 'differentiation enhancing factor', a HMG1 protein type, is an early step in murine erythroleukemia cell differentiation. FEBS Lett. 1995 Jul 24;368(3):466–470. doi: 10.1016/0014-5793(95)00716-m. [DOI] [PubMed] [Google Scholar]
  13. Melloni E., Sparatore B., Patrone M., Pessino A., Passalacqua M., Pontremoli S. Identity in molecular structure between "differentiation enhancing factor" of murine erythroleukemia cells and the 30 kD heparin-binding protein of developing rat brain. Biochem Biophys Res Commun. 1995 May 5;210(1):82–89. doi: 10.1006/bbrc.1995.1630. [DOI] [PubMed] [Google Scholar]
  14. Merenmies J., Pihlaskari R., Laitinen J., Wartiovaara J., Rauvala H. 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. J Biol Chem. 1991 Sep 5;266(25):16722–16729. [PubMed] [Google Scholar]
  15. Mignatti P., Morimoto T., Rifkin D. B. Basic fibroblast growth factor, a protein devoid of secretory signal sequence, is released by cells via a pathway independent of the endoplasmic reticulum-Golgi complex. J Cell Physiol. 1992 Apr;151(1):81–93. doi: 10.1002/jcp.1041510113. [DOI] [PubMed] [Google Scholar]
  16. Ogawa Y., Aizawa S., Shirakawa H., Yoshida M. Stimulation of transcription accompanying relaxation of chromatin structure in cells overexpressing high mobility group 1 protein. J Biol Chem. 1995 Apr 21;270(16):9272–9280. doi: 10.1074/jbc.270.16.9272. [DOI] [PubMed] [Google Scholar]
  17. Parkkinen J., Raulo E., Merenmies J., Nolo R., Kajander E. O., Baumann M., Rauvala H. Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. J Biol Chem. 1993 Sep 15;268(26):19726–19738. [PubMed] [Google Scholar]
  18. Patrone M., Pessino A., Passalacqua M., Sparatore B., Melloni E., Pontremoli S. Correlation between levels of delta protein kinase C and resistance to differentiation in murine erythroleukemia cells. Biochem Biophys Res Commun. 1996 Mar 7;220(1):26–30. doi: 10.1006/bbrc.1996.0350. [DOI] [PubMed] [Google Scholar]
  19. Pontremoli S., Melloni E., Damiani G., Michetti M., Salamino F., Sparatore B., Horecker B. L. Binding of monoclonal antibody to cathepsin M located on the external surface of rabbit lysosomes. Arch Biochem Biophys. 1984 Aug 15;233(1):267–271. doi: 10.1016/0003-9861(84)90625-8. [DOI] [PubMed] [Google Scholar]
  20. Singer D., Cooper M., Maniatis G. M., Marks P. A., Rifkind R. A. Erythropoietic differentiation in colonies of cells transformed by Friend virus. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2668–2670. doi: 10.1073/pnas.71.7.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Singh J., Dixon G. H. High mobility group proteins 1 and 2 function as general class II transcription factors. Biochemistry. 1990 Jul 3;29(26):6295–6302. doi: 10.1021/bi00478a026. [DOI] [PubMed] [Google Scholar]
  22. Sparatore B., Passalacqua M., Patrone M., Pessino A., Melloni E., Pontremoli S. Differentiation of HL60 promyelocytic cells is promoted by a 'differentiation enhancing factor' produced by erythroleukemia cells. FEBS Lett. 1993 Nov 15;334(2):198–202. doi: 10.1016/0014-5793(93)81711-8. [DOI] [PubMed] [Google Scholar]
  23. Sparatore B., Patrone M., Passalacqua M., Melloni E., Pontremoli S. Differentiation of murine erythroleukemia cells by hexamethylenebisacetamide involves secretion and binding to membranes of a differentiation enhancing factor. Biochem Biophys Res Commun. 1991 Aug 30;179(1):153–160. doi: 10.1016/0006-291x(91)91348-g. [DOI] [PubMed] [Google Scholar]
  24. Sparatore B., Patrone M., Salamino F., Passalacqua M., Melloni E., Pontremoli S. A vincristine-resistant murine erythroleukemia cell line secretes a differentiation enhancing factor. Biochem Biophys Res Commun. 1990 Nov 30;173(1):156–163. doi: 10.1016/s0006-291x(05)81035-6. [DOI] [PubMed] [Google Scholar]
  25. Sparatore B., Pessino A., Patrone M., Passalacqua M., Melloni E., Pontremoli S. Role of delta-PKC on the differentiation process of murine erythroleukemia cells. Biochem Biophys Res Commun. 1993 May 28;193(1):220–227. doi: 10.1006/bbrc.1993.1612. [DOI] [PubMed] [Google Scholar]
  26. Teo S. H., Grasser K. D., Hardman C. H., Broadhurst R. W., Laue E. D., Thomas J. O. Two mutations in the HMG-box with very different structural consequences provide insights into the nature of binding to four-way junction DNA. EMBO J. 1995 Aug 1;14(15):3844–3853. doi: 10.1002/j.1460-2075.1995.tb00054.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zollinger W. D., Dalrymple J. M., Artenstein M. S. Analysis of parameters affecting the solid phase radioimmunoassay quantitation of antibody to meningococcal antigens. J Immunol. 1976 Nov;117(5 PT2):1788–1798. [PubMed] [Google Scholar]

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