PML interacts with Myc, and Myc target gene expression is altered in PML-null fibroblasts

被引:37
作者
Cairo, S
De Falco, F
Pizzo, M
Salomoni, P
Pandolfi, PP
Meroni, G
机构
[1] TIGEM, I-80131 Naples, Italy
[2] Cornell Univ, Mem Sloan Kettering Canc Ctr, Mol Biol Program, New York, NY 10021 USA
[3] Cornell Univ, Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
关键词
Myc; PML; G1; phase; gene expression;
D O I
10.1038/sj.onc.1208338
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
c-myc is a well-known proto-oncogene encoding for a transcription factor that needs to be tightly regulated in order to preserve cell homeostasis. The Promyelocytic Leukaemia gene product PML plays an important role in cell growth and survival, and resides in discrete subnuclear structures called Nuclear Bodies ( NB). We performed comparative analysis of the expression of 40 Myc target genes and of Myc binding to their regulatory regions both in wild-type and PML knockout cells. We demonstrate that if PML is absent, despite Myc binding to the DNA regulatory sequences is unchanged, the expression pro. le of several Myc target genes is altered. PML is largely involved in gene regulation, via recruitment of several transcription factors and cofactors to the NB. Consistently, we show that Myc partially localizes to the NB and physically interacts with PML, and that this localization depends on Myc expression levels. As deregulation occurs to both activated and repressed Myc target genes, we propose that PML influences Myc transcriptional activity through a mechanism that involves the control of Myc post-translational modifications.
引用
收藏
页码:2195 / 2203
页数:9
相关论文
共 43 条
  • [21] Recurring chromosomal abnormalities in leukemia in PML-RARA transgenic mice parallel human acute promyelocytic leukemia
    Le Beau, MM
    Bitts, S
    Davis, EM
    Kogan, SC
    [J]. BLOOD, 2002, 99 (08) : 2985 - 2991
  • [22] Reconstructing MYC
    Levens, DL
    [J]. GENES & DEVELOPMENT, 2003, 17 (09) : 1071 - 1077
  • [23] PML SUPPRESSES ONCOGENIC TRANSFORMATION OF NIH/3T3 CELLS BY ACTIVATED NEU
    LIU, JH
    MU, ZM
    CHANG, KS
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (06) : 1965 - 1973
  • [24] The basic region/helix-loop-helix/leucine zipper domain of Myc proto-oncoproteins:: Function and regulation
    Lüscher, B
    Larsson, LG
    [J]. ONCOGENE, 1999, 18 (19) : 2955 - 2966
  • [25] Function and regulation of the transcription factors of the Mye/Max/Mad network
    Lüscher, B
    [J]. GENE, 2001, 277 (1-2) : 1 - 14
  • [26] Proteins associated with the promyelocytic leukemia gene product (PML)-containing nuclear body move to the nucleolus upon inhibition of proteasome-dependent protein degradation
    Mattsson, K
    Pokrovskaja, K
    Kiss, C
    Klein, G
    Szekely, L
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (03) : 1012 - 1017
  • [27] Möller A, 2003, CANCER RES, V63, P4310
  • [28] Recruitment of NBS1 into PML oncogenic domains via interaction with SP100 protein
    Naka, K
    Ikeda, K
    Motoyama, N
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 299 (05) : 863 - 871
  • [29] MYC oncogenes and human neoplastic disease
    Nesbit, CE
    Tersak, JM
    Prochownik, EV
    [J]. ONCOGENE, 1999, 18 (19) : 3004 - 3016
  • [30] The Mad and Myc basic domains are functionally equivalent
    Nikiforov, MA
    Popov, N
    Kotenko, I
    Henriksson, M
    Cole, MD
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (13) : 11094 - 11099