Identification of a large Myc-binding protein that contains RCC1-like repeats

Qingbin Guo1, Jingwu Xie1, Chi V. Dang1, Edison T. Liu1, J. Michael Bishop1
1G. W. Hooper Foundation and Cancer Research Institute, University of California, San Francisco, CA 94143; Section of Cellular and Molecular Oncogenesis, Division of Clinical Science, National Cancer Institute, Bethesda, MD 20892; and Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205

Tóm tắt

The protooncogene MYC plays an important role in the regulation of cellular proliferation, differentiation, and apoptosis and has been implicated in a variety of human tumors. MYC and the closely related MYCN encode highly conserved nuclear phosphoproteins (Myc and NMyc) that apparently function as transcription factors in the cell. We have identified a large and highly conserved nuclear protein that interacts directly with the transcriptional activating domain of Myc (designated “protein associated with Myc” or Pam). Pam contains an extended amino acid sequence with similarities to a protein known as regulator of chromosome condensation (RCC1), which may play a role in the function of chromatin. The gene encoding Pam ( PAM ) is expressed in all of the human tissue examined, but expression is exceptionally abundant in brain and thymus. Pam binds specifically to Myc, but not NMyc. The region in Myc required for binding to Pam includes a domain that is essential for the function of Myc and that is frequently mutated in Burkitt’s lymphomas. PAM is located within a 300-kb region on chromosome 13q22.

Từ khóa


Tài liệu tham khảo

K B Marcu, S A Bossone, A J Patel Annu Rev Biochem 61, 809–860 (1992).

C V Dang, L A Lee c-Myc Function in Neoplasia (Landes, Austin, TX, 1995).

M Henriksson, B Lüscher Adv Cancer Res 68, 109–182 (1996).

E M Blackwood, R N Eisenman Science 251, 1211–1217 (1991).

A L Roy, C Carruthers, T Gutjahr, R G Roeder Nature (London) 365, 359–361 (1993).

A Shrivastava, S Saleque, V Kalpana, S Artandi, S P Goff, K Calame Science 262, 1889–1892 (1993).

S Gaubatz, A Imhof, R Dosch, O Werner, P Mitchell, R Buettner, M Eilers EMBO J 14, 1508–1519 (1995).

W Gu, K Bhatia, I T Magrath, C V Dang, R Dalla-Favera Science 264, 251–254 (1994).

D Sakamuro, K J Elliott, R Wechsler-Reya, G C Prendergast Nat Genet 14, 69–77 (1996).

S Maheswaran, H Lee, G E Sonenshein Mol Cell Biol 14, 1147–1152 (1994).

S Gupta, R J Davis FEBS Lett 353, 281–285 (1994).

N Alexandrova, J Niklinski, V Bliskovsky, G A Otterson, M Blake, F J Kaye, M Zajac-Kaye Mol Cell Biol 15, 5188–5195 (1995).

T Klockars, M Savukoski, J Isosomppi, M Laan, I Järvelä, K Petrukhin, A Palotie, L Peltonen Genomics 35, 71–78 (1996).

J Stone, T De Lange, G Ramsay, E Jakobovits, J M Bishop, H Varmus, W Lee Mol Cell Biol 7, 1697–1709 (1987).

G Ramsay, L Stanton, M Schwab, J M Bishop Mol Cell Biol 6, 4450–4457 (1986).

M A Blanar, W J Rutter Science 256, 1014–1018 (1992).

J Sambrook, E F Fritsch, T Maniatis Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. Press, 2nd Ed., Plainview, NY, 1989).

H M Albertsen, H Abderrahim, H M Cann, J Dausset, D Paslier, D Cohen Proc Natl Acad Sci USA 87, 4256–4260 (1990).

J Figge, T F Smith Nature (London) 334, 109 (1988).

M Dasso Trends Biochem Sci 18, 96–101 (1993).

L Renault, N Nassar, I Vetter, J Becker, C Klebe, M Roth, A Wittinghofer Nature (London) 392, 97–101 (1998).

T Klockars, J Isosomppi, M Laan, A Palotie, L Peltonen Genomics 44, 355–357 (1997).

A Ma, T Moroy, R Collum, H Weintraub, F W Alt, T K Blackwell Oncogene 8, 1093–1098 (1993).

A Wenzel, C Cziepluch, U Hamann, J Schurmann, M Schwab EMBO J 10, 3703–3712 (1991).

F Cavalieri, M Goldfarb Oncogene 2, 289–291 (1987).

M Eilers, D Picard, K R Yamamoto, J M Bishop Nature (London) 340, 66–68 (1989).

M Schwab, J M Bishop Proc Natl Acad Sci USA 85, 9585–9589 (1988).

M B Small, N Hay, M Schwab, J M Bishop Mol Cell Biol 7, 1638–1645 (1987).

M Schwab, H E Varmus, J M Bishop Nature (London) 316, 160–162 (1985).

K M Downs, G R Martin, J M Bishop Genes Dev 3, 860–869 (1989).

K Kato, A Kanamori, Y Wakamatsu, S Sawai, H Kondos Dev Growth Differ 33, 29–36 (1991).

U Hirning, P Schmid, W A Schulz, G Rettenberger, H Hameister Mech Dev 33, 119–125 (1991).

B R Stanton, A S Perkins, L Tessarollo, D A Sassoon, L F Parada Genes Dev 6, 2235–2247 (1992).

J Charron, B A Malynn, P Fisher, V Stewart, L Jeannotte, S P Goff, E J Robertson, F W Alt Genes Dev 6, 2248–2257 (1992).

A C Davis, M Wims, G D Spotts, S R Hann, A Bradley Genes Dev 4, 671–682 (1993).