The retinoblastoma gene product RB stimulates Sp1-mediated transcription by liberating Sp1 from a negative regulator.
The retinoblastoma gene product RB stimulates Sp1-mediated transcription by liberating Sp1 from a negative regulator.
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视网膜母细胞瘤基因产物 RB 通过从负调节因子中释放 Sp1 来刺激 Sp1 介导的转录。
DOI：
10.1128/mcb.14.7.4380-4389.1994
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发表时间：
1994
影响因子：
5.3
通讯作者：
Chiu,R
中科院分区：
文献类型：
--
作者：
Chen,LI;Nishinaka,T;Kwan,K;Kitabayashi,I;Yokoyama,K;Fu,YH;Grünwald,S;Chiu,R
Studies have demonstrated that the retinoblastoma susceptibility gene product, RB, can either positively or negatively regulate expression of several genes throughcis-acting elements in a cell-type-dependent manner. The nucleotide sequence of the retinoblastoma control element (RCE) motif, GCCACC or CCACCC, and the Spl consensus binding sequence, CCGCCC, can confer equal responsiveness to RB. Here, we report that RB activates transcription of the c-jungene through the Spl-binding site within the c-junpromoter. Preincubation of crude nuclear extracts with monoclonal antibodies to RB results in reduction of Spl complexes in a mobility shift assay, while addition of recombinant RB in mobility shift assay mixtures with CCL64 cell extracts leads to an enhancement of DNA-binding activity of Spl. These results suggest that RB is directly or indirectly involved in Spl-DNA binding activity. A mechanism by which RB regulates transactivation is indicated by our detection of a heat-labile and protease-sensitive Spl negative regulator(s) (Spl-I) that specifically inhibits Spl binding to a c-junSpl site. This inhibition is reversed by addition of recombinant RB protein, suggesting that RB stimulates Spl-mediated transactivation by liberating Spl from Spl-I. Additional evidence for Spl-I involvement in Spl-mediated transactivation was demonstrated by cotransfection of RB, GAL4-Spl, and a GAL4-responsive template into CV-1 cells. Finally, we have identified Spl-I, a ~20-kDa protein(s) that inhibits the Spl complexes from binding to DNA and that is also an RB-associated protein. These findings provide evidence for a functional link between two distinct classes of oncoproteins, RB and c-Jun, that are involved in the control of cell growth, and also define a novel mechanism for the regulation of c-junexpression.
