Larsson L G, Pettersson M, Oberg F, Nilsson K, Lüscher B
Institut für Molekularbiologie, Medizinische Hochschule Hannover, Germany.
Oncogene. 1994 Apr;9(4):1247-52.
The Myc proto-oncoprotein family is considered to play an important role in the control of cell growth and differentiation. It appears that the interaction of Myc with its heterodimeric partner Max is essential for Myc function. Recently two other partners of Max, called Mad and Mxi1, have been identified. In an effort to gain insight into the network of these four proteins we have started to analyse the expression of the c-myc, max, mad and mxi1 genes at the mRNA level during hematopoietic cell growth and differentiation. In the human myeloid cell lines U-937, HL-60 and ML-1 c-myc expression was down-regulated as shown previously after induction of differentiation, whereas the expression of max was only slightly affected. In contrast to these two genes the expression of mad was induced upon differentiation in the three cell lines by TPA, retinoic acid, vitamin D3, dimethyl sulfoxide, and interferon-gamma and remained elevated for at least 3 days. A kinetic analysis showed that the induction of mad in U-937 in response to TPA was rapid (15 min) and at least in part transcriptional, reminiscent of immediate early genes. The expression of mxi1 was induced in U-937 by some inducers but not in HL-60 or ML-1. Its induction occurred slowly, peaking around 48 h. These analysis thus suggest that the expression of mad and c-myc is inversely regulated during induced hematopoietic differentiation.
Myc原癌蛋白家族被认为在细胞生长和分化的调控中起重要作用。Myc与其异二聚体伙伴Max的相互作用似乎对Myc功能至关重要。最近，Max的另外两个伙伴，即Mad和Mxi1，已被鉴定出来。为了深入了解这四种蛋白质的网络，我们开始分析造血细胞生长和分化过程中c-myc、max、mad和mxi1基因在mRNA水平的表达。在人髓系细胞系U-937、HL-60和ML-1中，如先前诱导分化后所示，c-myc表达下调，而max的表达仅受到轻微影响。与这两个基因不同，在三种细胞系中，TPA、视黄酸、维生素D3、二甲基亚砜和干扰素-γ诱导分化时，mad的表达被诱导，并至少持续升高3天。动力学分析表明，U-937中TPA诱导mad的速度很快（15分钟），且至少部分是转录水平的，这让人联想到即刻早期基因。U-937中一些诱导剂可诱导mxi1的表达，但HL-60或ML-1中则不然。其诱导过程缓慢，在48小时左右达到峰值。因此，这些分析表明，在诱导的造血分化过程中，mad和c-myc的表达受到相反的调节。
