TBLR1 regulates the expression of nuclear hormone receptor co-repressors.
TBLR1 regulates the expression of nuclear hormone receptor co-repressors.
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DOI：
10.1186/1471-2121-7-31
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发表时间：
2006-08-07
期刊：
影响因子：
--
通讯作者：
Basch RS
中科院分区：
文献类型：
--
作者：
Zhang XM;Chang Q;Zeng L;Gu J;Brown S;Basch RS
转录受激活子和抑制子复杂相互作用的调节。阻遏效应物是大的多聚体复合物，其含有结合到转录因子的阻遏蛋白和实际上通过抑制基础转录机器或通过募集染色质修饰酶来介导转录沉默的许多共阻遏物。TBLR 1 [GenBank：NM 024665]是核激素转录因子的共阻遏物。一个高度保守的基因编码一个小家族的蛋白质分子。不同的异构体是由不同的外显子利用产生的。虽然主要形式的ORF仅包含1545 bp，但人类基因在染色体3q上占据约200 kb的基因组DNA，并包含16个外显子。基因组序列与推定的DC 42 [基因库：NM 030921]基因座重叠。小鼠同源物在结构上相似，也位于3号染色体上。TBLR 1与位于X和Y染色体上的TBL 1X和TBL 1 Y密切相关（在mRNA水平上79%同源性）。TBLR 1的表达与TBL 1的表达重叠但不同。TBLR 1的可变剪接形式已在人类材料中得到证实，并且它也具有独特的表达模式。TBLR 1和同源基因与调节核激素受体家族转录因子的蛋白质相互作用。在静息细胞中，TBLR 1主要在细胞质中，但在扰动后，蛋白质易位到细胞核。TBLR 1与SMRT共沉淀，SMRT是核激素受体的共抑制物，并在HDAC 3的抗血清免疫沉淀的复合物中共沉淀。工程化以过表达TBLR 1或N-和C-末端缺失变体的细胞具有升高的内源性N-CoR水平。TBLR 1和SMRT的共转染导致SMRT的表达增加。这种共阻遏物经历了泛素介导的降解，我们认为TBLR 1稳定共阻遏物是因为一种新的机制，保护它们免受降解。TBLR 1的瞬时过表达导致生长停滞。TBLR 1是一种多功能的转录辅阻遏物。这个分子家族的结构是高度保守的，并且在所有真核生物中都发现了密切相关的辅阻遏物。辅阻遏物表达的调节和随之而来的转录沉默的改变在分化的调节中起着重要作用。
Transcription is regulated by a complex interaction of activators and repressors. The effectors of repression are large multimeric complexes which contain both the repressor proteins that bind to transcription factors and a number of co-repressors that actually mediate transcriptional silencing either by inhibiting the basal transcription machinery or by recruiting chromatin-modifying enzymes. TBLR1 [GenBank: NM024665] is a co-repressor of nuclear hormone transcription factors. A single highly conserved gene encodes a small family of protein molecules. Different isoforms are produced by differential exon utilization. Although the ORF of the predominant form contains only 1545 bp, the human gene occupies ~200 kb of genomic DNA on chromosome 3q and contains 16 exons. The genomic sequence overlaps with the putative DC42 [GenBank: NM030921] locus. The murine homologue is structurally similar and is also located on Chromosome 3. TBLR1 is closely related (79% homology at the mRNA level) to TBL1X and TBL1Y, which are located on Chromosomes X and Y. The expression of TBLR1 overlaps but is distinct from that of TBL1. An alternatively spliced form of TBLR1 has been demonstrated in human material and it too has an unique pattern of expression. TBLR1 and the homologous genes interact with proteins that regulate the nuclear hormone receptor family of transcription factors. In resting cells TBLR1 is primarily cytoplasmic but after perturbation the protein translocates to the nucleus. TBLR1 co-precipitates with SMRT, a co-repressor of nuclear hormone receptors, and co-precipitates in complexes immunoprecipitated by antiserum to HDAC3. Cells engineered to over express either TBLR1 or N- and C-terminal deletion variants, have elevated levels of endogenous N-CoR. Co-transfection of TBLR1 and SMRT results in increased expression of SMRT. This co-repressor undergoes ubiquitin-mediated degradation and we suggest that the stabilization of the co-repressors by TBLR1 occurs because of a novel mechanism that protects them from degradation. Transient over expression of TBLR1 produces growth arrest. TBLR1 is a multifunctional co-repressor of transcription. The structure of this family of molecules is highly conserved and closely related co-repressors have been found in all eukaryotic organisms. Regulation of co-repressor expression and the consequent alterations in transcriptional silencing play an important role in the regulation of differentiation.
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F-box蛋白家族。
影响因子：
12.3
作者：
Kipreos, E T;Pagano, M
通讯作者：
Pagano, M
影响因子：
64.8
作者：
HORLEIN, AJ;NAAR, AM;ROSENFELD, MG
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ROSENFELD, MG
影响因子：
64.8
作者：
CHEN, JD;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
9.8
作者：
Bassi, MT;Ramesar, RS;Borsani, G
通讯作者：
Borsani, G
影响因子：
64.5
作者：
Jepsen, K;Hermanson, O;Rosenfeld, MG
通讯作者：
Rosenfeld, MG