A critical role in structure-specific DNA binding for the acetylatable lysine residues in HMGB1

2008 ◽  
Vol 411 (3) ◽  
pp. 553-561 ◽  
Author(s):  
René Assenberg ◽  
Michelle Webb ◽  
Edward Connolly ◽  
Katherine Stott ◽  
Matthew Watson ◽  
...  
Keyword(s):  
Dna Binding ◽  
Critical Role ◽  
High Mobility ◽  
Full Length ◽  
High Mobility Group Protein ◽  
Bent Dna ◽  
Double Mutation ◽  
Lysine Residues ◽  
Group Protein

The structure-specific DNA-binding protein HMGB1 (high-mobility group protein B1) which comprises two tandem HMG boxes (A and B) and an acidic C-terminal tail, is acetylated in vivo at Lys2 and Lys11 in the A box. Mutation to alanine of both residues in the isolated A domain, which has a strong preference for pre-bent DNA, abolishes binding to four-way junctions and 88 bp DNA minicircles. The same mutations in full-length HMGB1 also abolish its binding to four-way junctions, and binding to minicircles is substantially impaired. In contrast, when the acidic tail is absent (AB di-domain) there is little effect of the double mutation on four-way junction binding, although binding to minicircles is reduced ∼15-fold. Therefore it appears that in AB the B domain is able to substitute for the non-functional A domain, whereas in full-length HMGB1 the B domain is masked by the acidic tail. In no case does single substitution of Lys2 or Lys11 abolish DNA binding. The double mutation does not significantly perturb the structure of the A domain. We conclude that Lys2 and Lys11 are critical for binding of the isolated A domain and HMGB1 to distorted DNA substrates.

scholarly journals The RAG1 Homeodomain Recruits HMG1 and HMG2 To Facilitate Recombination Signal Sequence Binding and To Enhance the Intrinsic DNA-Bending Activity of RAG1-RAG2

1999 ◽  
Vol 19 (10) ◽  
pp. 6532-6542 ◽  
Author(s):  
Vassilis Aidinis ◽  
Tiziana Bonaldi ◽  
Monica Beltrame ◽  
Sandro Santagata ◽  
Marco E. Bianchi ◽  
...  
Keyword(s):  
Signal Sequence ◽  
Specific Binding ◽  
High Mobility ◽  
Recombination Reaction ◽  
High Mobility Group Protein ◽  
Bent Dna ◽  
Recombination Signal ◽  
Group Protein

ABSTRACT V(D)J recombination is initiated by the specific binding of the RAG1-RAG2 (RAG1/2) complex to the heptamer-nonamer recombination signal sequences (RSS). Several steps of the V(D)J recombination reaction can be reconstituted in vitro with only RAG1/2 plus the high-mobility-group protein HMG1 or HMG2. Here we show that the RAG1 homeodomain directly interacts with both HMG boxes of HMG1 and HMG2 (HMG1,2). This interaction facilitates the binding of RAG1/2 to the RSS, mainly by promoting high-affinity binding to the nonamer motif. Using circular-permutation assays, we found that the RAG1/2 complex bends the RSS DNA between the heptamer and nonamer motifs. HMG1,2 significantly enhance the binding and bending of the 23RSS but are not essential for the formation of a bent DNA intermediate on the 12RSS. A transient increase of HMG1,2 concentration in transfected cells increases the production of the final V(D)J recombinants in vivo.

scholarly journals The High Mobility Group Protein 1 Enhances Binding of the Estrogen Receptor DNA Binding Domain to the Estrogen Response Element

1998 ◽  
Vol 12 (5) ◽  
pp. 664-674 ◽  
Author(s):  
Lorene E. Romine ◽  
Jennifer R. Wood ◽  
LuAnne A. Lamia ◽  
Paul Prendergast ◽  
Dean P. Edwards ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Dna Binding ◽  
High Mobility ◽  
High Mobility Group ◽  
Estrogen Response Element ◽  
Dna Binding Domain ◽  
High Mobility Group Protein ◽  
Response Element ◽  
Estrogen Response ◽  
Group Protein

Abstract We have examined the ability of the high-mobility group protein 1 (HMG1) to alter binding of the estrogen receptor DNA-binding domain (DBD) to the estrogen response element (ERE). HMG1 dramatically enhanced binding of purified, bacterially expressed DBD to the consensus vitellogenin A2 ERE in a dose-dependent manner. The ability of HMG1 to stabilize the DBD-ERE complex resulted in part from a decrease in the dissociation rate of the DBD from the ERE. Antibody supershift experiments demonstrated that HMG1 was also capable of forming a ternary complex with the ERE-bound DBD in the presence of HMG1-specific antibody. HMG1 did not substantially affect DBD-ERE contacts as assessed by methylation interference assays, nor did it alter the ability of the DBD to induce distortion in ERE-containing DNA fragments. Because HMG1 dramatically enhanced estrogen receptor DBD binding to the ERE, and the DBD is the most highly conserved region among the nuclear receptor superfamily members, HMG1 may function to enhance binding of other nuclear receptors to their respective response elements and act in concert with coactivator proteins to regulate expression of hormone-responsive genes.

scholarly journals Changes in quantities of high-mobility-group protein 1 in oviduct cellular fractions after oestrogen stimulation

1981 ◽  
Vol 198 (1) ◽  
pp. 85-90 ◽  
Author(s):  
C T Teng ◽  
C S Teng
Keyword(s):  
Microsomal Fraction ◽  
High Mobility ◽  
Quantitative Change ◽  
High Mobility Group ◽  
Nuclear Fraction ◽  
Hmg Proteins ◽  
High Mobility Group Protein ◽  
Group Protein ◽  
Oviduct Cell

Antiserum against chick oviduct high-mobility-group protein 1 (HMG 1) has been induced in the rabbit. With this antiserum, immunobiochemical techniques have been used to probe the quantitative change of HMG 1 in the cellular fractions of chick oviduct before or after oestrogen stimulation. HMG 1 is detectable in the cytosol, microsomal and nuclear fraction of the chick oviduct cell. After administration of oestrogen to young chicks in vivo for 5 days, the quantity of HMG 1 is increased 4-fold in the cytosol, 3.5-fold in the microsomal fraction and 1.6-fold in the nuclear fraction. The finding of large amounts of HMG 1 in cytoplasm of oviduct cell is not likely due to its leakage from the nucleus. We anticipate that HMG 1 is synthesized in the cytoplasm and then transported into the nucleus. The synthesis and transportation of HMG proteins is probably regulated by oestrogen.

scholarly journals High Mobility Group Protein-B1 Interacts with Sterol Regulatory Element-binding Proteins to Enhance Their DNA Binding

2005 ◽  
Vol 280 (30) ◽  
pp. 27523-27532 ◽  
Author(s):  
Yuho Najima ◽  
Naoya Yahagi ◽  
Yoshinori Takeuchi ◽  
Takashi Matsuzaka ◽  
Motohiro Sekiya ◽  
...  
Keyword(s):  
Dna Binding ◽  
Binding Proteins ◽  
Regulatory Element ◽  
High Mobility ◽  
High Mobility Group ◽  
High Mobility Group Protein ◽  
Sterol Regulatory Element ◽  
Group Protein

scholarly journals The Activity of Mammalian brm/SNF2α Is Dependent on a High-Mobility-Group Protein I/Y-Like DNA Binding Domain

1999 ◽  
Vol 19 (6) ◽  
pp. 3931-3939 ◽  
Author(s):  
Brigitte Bourachot ◽  
Moshe Yaniv ◽  
Christian Muchardt
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
High Mobility ◽  
High Mobility Group ◽  
Binding Motif ◽  
High Mobility Group Protein ◽  
Interaction Domain ◽  
Dna Binding Domains ◽  
Binding Domains ◽  
Group Protein

ABSTRACT The mammalian SWI-SNF complex is a chromatin-remodelling machinery involved in the modulation of gene expression. Its activity relies on two closely related ATPases known as brm/SNF2α and BRG-1/SNF2β. These two proteins can cooperate with nuclear receptors for transcriptional activation. In addition, they are involved in the control of cell proliferation, most probably by facilitating p105Rb repression of E2F transcriptional activity. In the present study, we have examined the ability of various brm/SNF2α deletion mutants to reverse the transformed phenotype ofras-transformed fibroblasts. Deletions within the p105Rb LXCXE binding motif or the conserved bromodomain had only a moderate effect. On the other hand, a 49-amino-acid segment, rich in lysines and arginines and located immediately downstream of the p105Rb interaction domain, appeared to be essential in this assay. This region was also required for cooperation of brm/SNF2α with the glucocorticoid receptor in transfection experiments, but only in the context of a reporter construct integrated in the cellular genome. The region has homology to the AT hooks present in high-mobility-group protein I/Y DNA binding domains and is required for the tethering of brm/SNF2α to chromatin.

scholarly journals Knockdown of MSI2 inhibits metastasis by interacting with caveolin-1 and inhibiting its ubiquitylation in human NF1-MPNST cells

2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Kang Yang ◽  
Jianwei Du ◽  
Dai Shi ◽  
Feng Ji ◽  
Yong Ji ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
High Mobility ◽  
Neurofibromatosis Type ◽  
Migration And Invasion ◽  
High Mobility Group Protein ◽  
Mesenchymal Transition ◽  
Caveolin 1 ◽  
Group Protein

AbstractMalignant peripheral nerve sheath tumours (MPNSTs) are highly aggressive Schwann cell-derived sarcomas, and they are either associated with neurofibromatosis type 1 (NF1) or sporadic. Our previous study found that high mobility group protein A2 (HMGA2) regulates NF1-MPNST growth through Musashi-2 (MSI2); however, whether MSI2 regulates MPNST metastasis and what the mechanism is remain unclear. Here, we demonstrated that the protein caveolin-1 (CAV1) directly interacts with MSI2 in human NF1-MPNST cells. Moreover, we discovered that knockdown of MSI2 induces CAV1 protein expression by inhibiting its ubiquitylation level in NF1-MPNSTs. In addition, CAV1 mediates the suppressive function of MSI2 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to reveal the potential mechanisms of MSI2 as a target of antimetastatic treatment for human NF1-MPNST.

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