Differential Regulation of c-Myb-induced Transcription Activation by a Phosphorylation Site in the Negative Regulatory Domain*
Differential Regulation of c-Myb-induced Transcription Activation by a Phosphorylation Site in the Negative Regulatory Domain*
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负调控域中磷酸化位点对 c-Myb 诱导的转录激活的差异调节*
DOI：
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发表时间：
1996
影响因子：
4.8
通讯作者：
T. Bender
中科院分区：
文献类型：
--
作者：
M. Miglarese;A. Richardson;N. Aziz;T. Bender
原癌基因c-myb编码一个高度保守的75-89 kDa转录因子，它包含三个功能结构域，即氨基末端DNA结合域(DBD)、中心酸性反式激活结构域和羧基末端负调控结构域(NRD)。两种急性转化逆转录病毒，禽成髓细胞增多症病毒和E26白血病病毒，转导了部分c-myb并编码在DBD和NRD中截断的Myb蛋白。在NRD内或附近存在着几个可能被Pro导向的丝氨酸/苏氨酸蛋白激酶磷酸化的保守位点，这表明磷酸化可能在调节c-Myb中发挥作用。我们先前已经证明，位于NRD的丝氨酸528是p42mapk的体外靶点。丝氨酸528在几个细胞系中被磷酸化，丝氨酸528替换为丙氨酸(S528A)导致Myb反式激活合成启动子的能力增强，该合成启动子包含五个拷贝的mim-1AMyb反应元件和一个最小的疱疹tk启动子。我们已经测试了S528A Myb反式激活一系列细胞靶向启动子的能力，并报告了丝氨酸替代丙氨酸增加了Myb激活CD34启动子转录的能力，但不能激活c-myc或mim-1启动子。这表明丝氨酸528的磷酸化可能对不同启动子上的c-Myb活性有不同的调节作用。C-Myb的DNA结合和多聚体活性似乎不受S528A替换的影响，提示丝氨酸528的磷酸化可能通过调节与其他蛋白质的相互作用来调节其对c-Myb转录反式激活活性的影响。
The c-myb protooncogene encodes a highly conserved 75-89-kDa transcription factor that contains three functional domains, an amino-terminal DNA binding domain (DBD), a central acidic transactivation domain, and a carboxyl-terminal negative regulatory domain (NRD). Two acute transforming retroviruses, avian myeloblastosis virus and the E26 leukemia virus, transduced portions of c-myb and encode Myb proteins that are truncated in both the DBD and the NRD. Several conserved potential sites for phosphorylation by proline-directed serine/threonine protein kinases reside in or near the NRD, suggesting that phosphorylation might play a role in regulating c-Myb. We have previously demonstrated that serine 528, located in the NRD, is a target for p42mapk in vitro. Serine 528 is phosphorylated in vivo in several cell lines, and substitution of serine 528 to alanine (S528A) resulted in an increased ability of Myb to transactivate a synthetic promoter containing five copies of the mim-1A Myb-responsive element and a minimal herpes tk promoter. We have tested the ability of S528A Myb to transactivate a series of cellular target promoters and report that the serine to alanine substitution increased the ability of Myb to activate transcription from the CD34 promoter but not the c-myc or mim-1 promoters. This suggests that phosphorylation of serine 528 may differentially regulate c-Myb activity at different promoters. The DNA binding and multimerization activities of c-Myb appear to be unaffected by the S528A substitution, suggesting that phosphorylation of serine 528 may mediate its effect on the transcription transactivating activity of c-Myb by regulating interactions with other proteins.
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影响因子：
10.5
作者：
通讯作者：
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粒细胞-巨噬细胞集落刺激因子、白介素-3 和钢因子诱导 p42 和 p44 MAP 激酶的快速酪氨酸磷酸化。
影响因子：
20.3
作者：
Okuda,K;Sanghera,JS;Pelech,SL;Kanakura,Y;Hallek,M;Griffin,JD;Druker,BJ
通讯作者：
Druker,BJ
影响因子：
56.9
作者：
SEGIL, N;ROBERTS, SB;HEINTZ, N
通讯作者：
HEINTZ, N
影响因子：
11.2
作者：
C. Griffin;S. Baylin
通讯作者：
C. Griffin;S. Baylin
DOI：
10.1073/pnas.83.11.3982
发表时间：
1986-06-01
影响因子：
11.1
作者：
REED, JC;ALPERS, JD;HOOVER, RG
通讯作者：
HOOVER, RG