Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins.
Role of the unique N-terminal domain of CtBP2 in determining the subcellular localisation of CtBP family proteins.
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DOI：
10.1186/1471-2121-7-35
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发表时间：
2006-09-25
期刊：
影响因子：
--
通讯作者：
Blaydes JP
中科院分区：
文献类型：
--
作者：
Bergman LM;Morris L;Darley M;Mirnezami AH;Gunatilake SC;Blaydes JP
CtBP1和CtBP2是转录共阻遏因子，通过募集染色质修饰因子来调节大量转录阻遏因子的活性。许多ctbp调节的蛋白参与与肿瘤发生相关的途径，包括TGF-β和Wnt信号通路和细胞周期调节因子，如RB/p130和HDM2，以及腺病毒E1A。CtBP1和CtBP2是高度相似的蛋白，尽管有证据表明它们的活性可以受到不同的调节，特别是通过控制它们的亚细胞定位。来自不同物种的CtBP2s含有一个独特的n端，在CtBP1中缺失，在控制蛋白的核质分布中起关键作用。这里我们展示了氨基酸（a.a。）CtBP2的4-14位基因直接引导CtBP2在不同来源的细胞系中几乎全核分布。虽然该序列与已知的核定位基序相似，但它不能驱动异源蛋白的核定位，而是作为p300乙酰转移酶依赖的核保留序列发挥作用。在这里，我们将CtBP2与a.a.4 - 14合作促进CtBP2核积累所需的区域定义为a.a.1 - 119。此外，我们发现CtBP2的a.a.a 120-445也可以促进CtBP2的核积累，而不依赖a.a.a 4-14。最后，CtBP1和CtBP2可以形成异源二聚体，我们发现与CtBP2的相互作用是CtBP1可以被招募到细胞核的一种机制。总之，这些发现代表了CtBP家族成员功能调控的关键区别，这可能对它们在发育、细胞分化和存活中的作用具有重要意义。
CtBP1 and CtBP2 are transcriptional co-repressors that modulate the activity of a large number of transcriptional repressors via the recruitment of chromatin modifiers. Many CtBP-regulated proteins are involved in pathways associated with tumorigenesis, including TGF-β and Wnt signalling pathways and cell cycle regulators such as RB/p130 and HDM2, as well as adenovirus E1A. CtBP1 and CtBP2 are highly similar proteins, although evidence is emerging that their activity can be differentially regulated, particularly through the control of their subcellular localisation. CtBP2s from diverse species contain a unique N-terminus, absent in CtBP1 that plays a key role in controlling the nuclear-cytoplasmic distribution of the protein. Here we show that amino acids (a.a.) 4–14 of CtBP2 direct CtBP2 into an almost exclusively nuclear distribution in cell lines of diverse origins. Whilst this sequence contains similarity to known nuclear localisation motifs, it cannot drive nuclear localisation of a heterologous protein, but rather has been shown to function as a p300 acetyltransferase-dependent nuclear retention sequence. Here we define the region of CtBP2 required to co-operate with a.a. 4–14 to promote CtBP2 nuclear accumulation as being within a.a. 1–119. In addition, we show that a.a. 120–445 of CtBP2 can also promote CtBP2 nuclear accumulation, independently of a.a. 4–14. Finally, CtBP1 and CtBP2 can form heterodimers, and we show that the interaction with CtBP2 is one mechanism whereby CtBP1 can be recruited to the nucleus. Together, these findings represent key distinctions in the regulation of the functions of CtBP family members that may have important implications as to their roles in development, and cell differentiation and survival.
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DOI：
10.1073/pnas.92.23.10467
发表时间：
1995-11-07
影响因子：
11.1
作者：
SCHAEPER, U;BOYD, JM;CHINADURAI, G
通讯作者：
CHINADURAI, G
影响因子：
5.3
作者：
Alpatov, R;Munguba, GC;Sugrue, SP
通讯作者：
Sugrue, SP
影响因子：
4.8
作者：
Koipally, J;Georgopoulos, K
通讯作者：
Georgopoulos, K
影响因子：
16
作者：
Lin, X;Sun, BH;Feng, XH
通讯作者：
Feng, XH
DOI：
10.1073/pnas.0830998100
发表时间：
2003-04-15
影响因子：
11.1
作者：
Grooteclaes, M;Deveraux, Q;Frisch, SM
通讯作者：
Frisch, SM