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

Identification of a large Myc-binding protein that contains RCC1-like repeats
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DOI:
10.1073/pnas.95.16.9172
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发表时间:
1998-08-04
影响因子:
11.1
通讯作者:
Bishop, JM
Bishop, JM
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Guo, QB;Xie, JW;Bishop, JM

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原癌基因MYC在细胞增殖、分化和凋亡的调节中起重要作用,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),其在细胞中显然作为转录因子起作用。我们已经鉴定了与Myc的转录激活结构域直接相互作用的大的且高度保守的核蛋白(命名为“与Mgc相关的蛋白”或Pam)。Pam含有与称为染色体凝聚调节因子(RCC 1)的蛋白质具有相似性的延伸的氨基酸序列,其可在染色质的功能中发挥作用。编码Pam(PAM)的基因在所检查的所有人体组织中表达,但在脑和胸腺中表达异常丰富,Pam特异性结合Myc,而不结合NMyc。MSc中与Pam结合所需的区域包括Myc功能所必需的结构域,该结构域在伯基特淋巴瘤中经常突变。PAM位于染色体13 q22上的300-kb区域内。
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 Mgc" or Pam). Pam contains an extended amino acid sequence with similarities to a protein known as regulator of chromosome condensation (RCC1), which mag 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 MSc 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.