Cell Signaling Technology

Product Pathways - TGF-beta/Smad Signaling

TRIM33 (E1N2Z) Rabbit mAb #13387

E3 Ligases   TIF1-gamma   TIF1gmma   TRIM-33   TRIM33  

No. Size Price
13387S 100 µl ( 10 western blots ) ¥3,100.00 现货查询 购买询价
13387 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human, Endogenous 150 Rabbit IgG

Species cross-reactivity is determined by western blot.

Applications Key: W=Western Blotting,

Homology

Species predicted to react based on 100% sequence homology: Bovine, Dog, Horse,

Specificity / Sensitivity

TRIM33 (E1N2Z) Rabbit mAb recognizes endogenous levels of total TRIM33 protein. Based upon sequence alignment, this antibody is predicted to react with TRIM33 isoforms A and B, but not with other TIF family members.

TRIM33 (E1N2Z) Rabbit mAb兔单抗可以识别内源性的总TRIM33蛋白。基于序列比对,预测该抗体能识别TRIM33亚型A和B,而不会与其他TIF家族成员发生交叉反应。

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human TRIM33 protein.

单克隆抗体由合成肽段免疫动物产生,该肽段与人TRIM33蛋白羧基末端邻近的氨基酸残基序列一致。

Western Blotting

Western Blotting

Western blot analysis of extracts from various cell lines using TRIM33 (E1N2Z) Rabbit mAb.

使用TRIM33 (E1N2Z) Rabbit mAb兔单抗对多种细胞提取物进行western blot分析。

Specificity

Specificity

Western blot analysis of extracts from 293T cells, transfected with 100 nM SignalSilence® Control siRNA (Unconjugated) #6568 (-), SignalSilence® TRIM33 siRNA I #13487 (+), or SignalSilence® siRNA II #13503 (+), using TRIM33 (E1N2Z) Rabbit mAb (upper) or GAPDH (D16H11) XP® Rabbit mAb #5174 (lower). The TRIM33 (E1N2Z) Rabbit mAb confirms silencing of TRIM33, while the GAPDH (D16H11) XP® Rabbit mAb is used as a loading control.

使用TRIM33 (E1N2Z) Rabbit mAb兔单抗(上)或GAPDH (D16H11) XP® Rabbit mAb #5174(下)对转染了100 nM SignalSilence® Control siRNA (未偶联) #6568 (-), SignalSilence® TRIM33 siRNA I (+), 或 SignalSilence® TRIM33 siRNA II #12440 (+)的293T细胞提取物进行western blot分析。TRIM33 (E1N2Z) Rabbit mAb用于确认TRIM33被敲除,GAPDH (D16H11) XP® Rabbit mAb用于确认上样量一致。

Background

The transcriptional intermediary factor 1 (TIF1) family represents a group of proteins with multiple histone-binding domains. In humans, this family comprises four proteins, TIF1α/TRIM24, TIF1β/TRIM28/KAP1, TIF1γ/TRIM33/Ectodermin, and TIF1δ/TRIM66, which are characterized by an amino-terminal tripartite motif (TRIM) domain consisting of a RING domain, two B boxes, a coiled-coil domain, and a carboxy-terminal PHD finger and bromodomain (1). Despite their similar overall structure, these proteins have diverse roles in transcriptional regulation. TIF1α functions as a ligand-dependent nuclear receptor coregulator and more recently has been implicated in regulating p53 stability (2). TIF1β is an intrinsic component of the N-CoR1 corepressor complex and the NuRD nucleosome-remodeling complex (3) and functions as a corepressor for Kruppel-associated box (KRAB) zinc-finger transcription factors (4). Furthermore, TIF1β promotes heterochromatin-mediated gene silencing formation by serving as a cofactor for heterochromatin protein HP1 (5). TIF1δ expression is restricted to the testis and has been shown to interact with HP1γ (6).

转录中介因子1 (TIF1)家族代表着一类有多个组蛋白结合结构与的蛋白。在人体中,该家族由四个蛋白组成,TIF1α/TRIM24, TIF1β/TRIM28/KAP1, TIF1γ/TRIM33/Ectodermin, 和TIF1δ/TRIM66,其特点是含有一个RING结构与,两个B 盒子,一个卷曲螺旋结构域和一个羧基端PHD finger和bromodomain组成的氨基末端tripartite motif (TRIM)结构域(1)。除了类似的结构,这些蛋白在转录调控中表现了多种功能。TIF1α功能为配体依赖性核受体的辅助调节因子,最近认为它涉及调节p53的稳定性(2)。TIF1β是N-COR1辅阻遏物复合物和NURD核小体重塑复合物的固有成分(3),用作Kruppel-associated box(KRAB)的锌指转录因子的辅阻遏物(4)。不仅如此,TIF1β作为异染色质蛋白HP1的辅助因子促进异染色质介导的基因沉默(5). TIF1δ的表达限制在睾丸中,并证明能和HP1γ相互作用(6)。

In contrast, the ubiquitous nuclear protein TRIM33 does not interact with either HP1 family members or chromatin-remodeling/modifying complexes. Rather, TRIM33 plays a pivotal role in signaling cascades driven by the TGF-β superfamily of ligands (7-9). A research study suggests that TRIM33 and Smad4 compete for binding to receptor phosphorylated Smad2/3 and that TRIM33-Smad2/3 and Smad4-Smad2/3 complexes complement one another in the TGF-β-dependent control of hematopoietic cell fate (9). Other studies, however, demonstrate that TRIM33 functions to repress signal relay by the TGF-β superfamily (7-8,10). Indeed, knockout of murine Trim33 results in embryonic lethality due to upregulated Nodal signaling (10). Mechanistically, TRIM33 functions as an E3-ubiquitin ligase and promotes monoubiquitination of Smad4, a modification that impairs its ability to associate with phospho-Smad2 (8). This negative regulatory mechanism is further substantiated by the discovery that TRIM33 disrupts transcriptionally competent Smad complexes on the promoter/enhancer regions of TGF-β-responsive genes by associating with specific epigenetic marks on histone H3, which is a requirement for activating TRIM33's monoubiquitin ligase activity toward Smad4 (11). In line with the ability of TRIM33 to regulate the development of different blood cell lineages, it was shown that loss of TRIM33 expression due to epigenetic silencing of its promoter contributes to the pathogenesis of chronic myelomonocytic leukemia (12).

广泛表达的核蛋白质TRIM33不与任一HP1家庭成员或染色质重构/修饰复合物相互作用。与此相反,TRIM33在TGF-β超家族的配体主导的信号级联反应中发挥了重要作用(7-9)。研究指出TRIM33和Smad4竞争结合受体磷酸化的受体Smad2/3,TRIM33-Smad2/3和Smad4-Smad2/3复合物在TGF-β依赖的造血细胞命运决定过程中功能互补(9)。但是其他研究证明了TRIM33抑制了TGF-β超家族的信号(7-8,10)。实际上,敲除小鼠的Trim33 会导致Nodal信号上升最终胚胎致死(10)。理论上,TRIM33作为一个E3泛素连接酶,会促进Smad4的单泛素化,这个修饰将削弱它和磷酸化Smad2结合的能力(8)。这个负调控机制进一步由TRIM33破坏竞争Smad复合物和TGF-β反应基因的启动子/增强子区域的结合能力而证实的,这个过程中TRIM33和表观遗传学标记组蛋白H3结合,组蛋白H3能够激活TRIM33对Smad4的单泛素化能力(11)。与TRIM33调节不同血细胞系发育的能力一致,TRIM33的表观遗传学沉默导致的表达缺失会引起慢性粒细胞白血病的症状(12)。

  1. Meroni, G. and Diez-Roux, G. (2005) Bioessays 27, 1147-57.
  2. Jain, A.K. and Barton, M.C. (2009) Cell Cycle 8, 3668-74.
  3. Underhill, C. et al. (2000) J Biol Chem 275, 40463-70.
  4. Schultz, D.C. et al. (2001) Genes Dev 15, 428-43.
  5. Groner, A.C. et al. (2010) PLoS Genet 6, e1000869.
  6. Khetchoumian, K. et al. (2004) J Biol Chem 279, 48329-41.
  7. Dupont, S. et al. (2005) Cell 121, 87-99.
  8. Dupont, S. et al. (2009) Cell 136, 123-35.
  9. He, W. et al. (2006) Cell 125, 929-41.
  10. Morsut, L. et al. (2010) Development 137, 2571-8.
  11. Agricola, E. et al. (2011) Mol Cell 43, 85-96.
  12. Aucagne, R. et al. (2011) J Clin Invest 121, 2361-70.

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