Hetero-oligomerization among the TIF family of RBCC/TRIM domain-containing nuclear cofactors: A potential mechanism for regulating the switch between coactivation and corepression
Hetero-oligomerization among the TIF family of RBCC/TRIM domain-containing nuclear cofactors: A potential mechanism for regulating the switch between coactivation and corepression
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DOI：
10.1016/s0022-2836(02)00477-1
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发表时间：
2002-07-12
影响因子：
5.6
通讯作者：
Rauscher, FJ
中科院分区：
文献类型：
--
作者：
Peng, HZ;Feldman, I;Rauscher, FJ
RING-B 盒状卷曲线圈 (RBCC) 基序（最近也重新命名为三部分基序 (TRIM)）是一种广泛分布的基序，被假设为蛋白质-蛋白质界面。辅阻遏物 KAP-1 的 RBCC/TRIM 结构域对于与转录阻遏物 KRAB 结构域直接相互作用是必要且充分的。 KAP-1-RBCC 的每个子结构域都直接参与寡聚化和/或配体识别。关于其他 TIF 家族成员的 RBCC/TRIM 结构域的功能或天然结合配体知之甚少。为了研究异源寡聚化是否可能是一种生物调节机制，我们评估了 TIF 家族成员（包括 KAP-1、TIF1α、TIF1gamma）和 RBCC/TRIM 家族成员（包括 PML1 和 MID1）的异源寡聚化潜力。我们通过生化方法使用杆状病毒和哺乳动物表达系统重建并表征了这些蛋白质的寡聚化。我们的数据表明 KAP-1、TIF1α 和 TIF1gamma 的 RBCC/TRIM 结构域以同源寡聚状态存在。然而，KAP-1 和其他 TIF 家族成员之间几乎没有串扰，这表明寡聚界面和配体识别的高度特异性本质上内置于 KAP-1 的 RBCC/TRIM 结构域中。最后，我们证明 TIF1alpha 与 TIF1gamma 相互作用，并且 TIF1gamma 的卷曲螺旋区域对于这种相互作用是必要的。 TIF1α 和 TIF1gamma 之间的异源寡聚化暗示了转录调控的潜在调控机制。 (C) 2002 Elsevier Science Ltd. 保留所有权利。
The RING-B box-coiled-coil (RBCC) motif (also re-named recently as the tripartite motif (TRIM)) is a widely distributed motif that is hypothesized to be a protein-protein interface. The RBCC/TRIM domain of the corepressor KAP-1 is both necessary and sufficient to interact directly with the transcription repressor KRAB domain. Each subdomain of the KAP-1-RBCC contributes directly to the oligomerization and/or ligand recognition. Little is known about the function or the natural binding ligands for the RBCC/TRIM domain of the other TIF family members. In order to investigate whether hetero-oligomerization might be a biological regulatory mechanism, we have evaluated the hetero-oligomerization potential of the TIF family members including KAP-1, TIF1alpha, TIF1gamma, and the RBCC/TRIM family members including PML1, and MID1. We have reconstituted and characterized the oligomerization for these proteins using baculovirus and mammalian expression systems by biochemical approaches. Our data indicate that the RBCC/TRIM domains of KAP-1, TIF1alpha and TIF1gamma exist in a homo-oligomeric state. However, there is little cross-talk between KAP-1 and other TIF family members, suggesting that a high degree of specificity for oligomerization interface and ligand recognition is intrinsically built into the RBCC/TRIM domain of KAP-1. Finally, we demonstrate that TIF1alpha interacts with TIF1gamma and the coiled-coil region of TIF1gamma is necessary for this interaction. The hetero-oligomerization between TIF1alpha and TIF1gamma implies a potential regulatory mechanism for transcriptional regulation. (C) 2002 Elsevier Science Ltd. All rights reserved.