Guo Q, Xie J, Dang C V, Liu E T, Bishop J M
G. W. Hooper Foundation, University of California, San Francisco, CA 94143, USA.
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9172-7. doi: 10.1073/pnas.95.16.9172.
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.
原癌基因MYC在细胞增殖、分化和凋亡的调控中发挥重要作用，并与多种人类肿瘤有关。MYC和密切相关的MYCN编码高度保守的核磷蛋白（Myc和NMyc），它们在细胞中显然作为转录因子发挥作用。我们鉴定出一种大型且高度保守的核蛋白，它直接与Myc的转录激活结构域相互作用（命名为“与Myc相关的蛋白”或Pam）。Pam包含一段与一种名为染色体凝聚调节因子（RCC1）的蛋白质相似的延伸氨基酸序列，RCC1可能在染色质功能中发挥作用。编码Pam的基因（PAM）在所检测的所有人类组织中均有表达，但在脑和胸腺中表达尤为丰富。Pam特异性结合Myc，而不结合NMyc。Myc中与Pam结合所需的区域包括一个对Myc功能至关重要且在伯基特淋巴瘤中经常发生突变的结构域。PAM位于13q22染色体上一个300 kb的区域内。
