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1.
Nucleic Acids Res ; 49(20): 11666-11689, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34718742

RESUMO

The inhibitor of DNA-binding 3 (ID3) is a transcriptional regulator that limits interaction of basic helix-loop-helix transcription factors with their target DNA sequences. We previously reported that ID3 loss is associated with mutational signatures linked to DNA repair defects. Here we demonstrate that ID3 exhibits a dual role to promote DNA double-strand break (DSB) repair, particularly homologous recombination (HR). ID3 interacts with the MRN complex and RECQL helicase to activate DSB repair and it facilitates RAD51 loading and downstream steps of HR. In addition, ID3 promotes the expression of HR genes in response to ionizing radiation by regulating both chromatin accessibility and activity of the transcription factor E2F1. Consistently, analyses of TCGA cancer patient data demonstrate that low ID3 expression is associated with impaired HR. The loss of ID3 leads to sensitivity of tumor cells to PARP inhibition, offering new therapeutic opportunities in ID3-deficient tumors.


Assuntos
Recombinação Homóloga , Proteínas Inibidoras de Diferenciação/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/genética , Linhagem Celular Tumoral , Quebras de DNA de Cadeia Dupla , Resistencia a Medicamentos Antineoplásicos , Fator de Transcrição E2F1/metabolismo , Células HEK293 , Humanos , Proteínas Inibidoras de Diferenciação/química , Masculino , Proteínas de Neoplasias/química , Inibidores de Poli(ADP-Ribose) Polimerases/toxicidade , Poli(ADP-Ribose) Polimerases/metabolismo , Rad51 Recombinase/metabolismo , RecQ Helicases/metabolismo
2.
Chembiochem ; 19(15): 1625-1629, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-29790640

RESUMO

NMR spectroscopy is one of the main techniques used for high-resolution studies of intrinsically disordered proteins (IDPs), permitting mapping of the structural and dynamic features of all the amino acids constituting the polypeptide at atomic resolution. Only proline residues are less straightforward to characterize because they lack any amide proton, thus rendering them not directly visible in the commonly used 2D 1 H,15 N correlation experiments. However, proline residues are highly abundant in IDPs and can mediate important functions. In this work we present an easy and effective way to obtain fingerprints of proline residues in IDPs at high resolution.


Assuntos
Proteínas Intrinsicamente Desordenadas/química , Prolina/análise , Sequência de Aminoácidos , Humanos , Proteínas Inibidoras de Diferenciação/química , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica
3.
J Biomol Struct Dyn ; 36(7): 1834-1852, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-28571517

RESUMO

Ptf1-p48 (Pancreas specific transcription factor 1a) is transcription regulatory protein known for the activation of exocrine specific genes. Downregulation of its expression formulates early stages of pancreatic adenocarcinoma as deduced by its association with oncogenic bHLH (Basic Helix-Loop-Helix) protein ID3 (Inhibitor of DNA binding 3) protein whose overexpression induces cytoplasmic mislocalization of Ptf1-p48. The precise mechanism and/or functional role of Ptf1-p48in promoting pancreatic cancer is vague. The structural features of the Ptf1-p48 and its dimerization with E47 (Transcription factor E2-alpha) and ID3 mediated by their HLH (Helix-Loop-Helix) domain were perceived through MD (Molecular Dynamics) simulations of 50 ns. The interactions formed by the HLH domain in both Ptf1-E47 and Ptf1-ID3 complexes are favored by the synergistic movement of their domain helices. Accordingly, in the Ptf1-E47 complex α7 of Ptf1-p48 and α1 helix of E47 along with the loop residues of their HLH domain exhibit transitions marked by inward movement toward each other and forms polar and charged interactions. In the Ptf1-ID3 complex, α8 of Ptf1-p48 moves toward the α3 helix of ID3 and forms hydrogen bonds. The interface analysis also reveals better interface in the Ptf1-p48 complex than the Ptf1-ID3 evident by energetics and number of hydrogen bonds. The interactions in each of these complexes, supported by angular displacement and mode vector analyzes, comprehensibly describe the considerable structural changes induced upon dimer formation. It thereby gives an insight into the interfaces that could help in designing of potential inhibitors for ID3 to curb the cancer cell growth.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Proteínas Inibidoras de Diferenciação/química , Fatores de Transcrição/química , Ligação de Hidrogênio , Simulação de Dinâmica Molecular , Domínios Proteicos
4.
Oncotarget ; 7(42): 68072-68085, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27487149

RESUMO

ID4, a helix loop helix transcriptional regulator has emerged as a tumor suppressor in prostate cancer. Epigenetic silencing of ID4 promotes prostate cancer whereas ectopic expression in prostate cancer cell lines blocks cancer phenotype. To directly investigate the anti-tumor property, full length human recombinant ID4 encapsulated in biodegradable Polycaprolactone/Maltodextrin (PCL-MD) nano-carrier was delivered to LNCaP cells in which the native ID4 was stably silenced (LNCaP(-)ID4). The cellular uptake of ID4 resulted in increased apoptosis, decreased proliferation and colony formation. Intratumoral delivery of PCL-MD ID4 into growing LNCaP(-)ID4 tumors in SCID mice significantly reduced the tumor volume compared to the tumors treated with chemotherapeutic Docetaxel. The study supports the feasibility of using nano-carrier encapsulated ID4 protein as a therapeutic. Mechanistically, ID4 may assimilate multiple regulatory pathways for example epigenetic re-programming, integration of multiple AR co-regulators or signaling pathways resulting in tumor suppressor activity of ID4.


Assuntos
Proteínas Inibidoras de Diferenciação/metabolismo , Nanopartículas/química , Neoplasias da Próstata/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Docetaxel , Portadores de Fármacos/química , Humanos , Proteínas Inibidoras de Diferenciação/química , Proteínas Inibidoras de Diferenciação/genética , Masculino , Camundongos SCID , Nanopartículas/administração & dosagem , Poliésteres/química , Polissacarídeos/química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Interferência de RNA , Taxoides/farmacologia , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética
5.
Biophys J ; 110(2): 372-381, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26789760

RESUMO

Here, we present a structural and dynamic description of CBP-ID4 at atomic resolution. ID4 is the fourth intrinsically disordered linker of CREB-binding protein (CBP). In spite of the largely disordered nature of CBP-ID4, NMR chemical shifts and relaxation measurements show a significant degree of α-helix sampling in the protein regions encompassing residues 2-25 and 101-128 (1852-1875 and 1951-1978 in full-length CBP). Proline residues are uniformly distributed along the polypeptide, except for the two α-helical regions, indicating that they play an active role in modulating the structural features of this CBP fragment. The two helical regions are lacking known functional motifs, suggesting that they represent thus-far uncharacterized functional modules of CBP. This work provides insights into the functions of this protein linker that may exploit its plasticity to modulate the relative orientations of neighboring folded domains of CBP and fine-tune its interactions with a multitude of partners.


Assuntos
Proteína de Ligação a CREB/química , Proteínas Inibidoras de Diferenciação/química , Simulação de Dinâmica Molecular , Motivos de Aminoácidos , Sequência de Aminoácidos , Humanos , Dados de Sequência Molecular , Estrutura Terciária de Proteína
6.
Biochim Biophys Acta ; 1855(1): 92-103, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25512197

RESUMO

Highly conserved Inhibitors of DNA-Binding (ID1-ID4) genes encode multi-functional proteins whose transcriptional activity is based on dominant negative inhibition of basic helix-loop-helix (bHLH) transcription factors. Initial animal models indicated a degree of compensatory overlap between ID genes such that deletion of multiple ID genes was required to generate easily recognizable phenotypes. More recently, new model systems have revealed alterations in mice harboring deletions in single ID genes suggesting complex gene and tissue specific functions for members of the ID gene family. Because ID genes are highly expressed during development and their function is associated with a primitive, proliferative cellular phenotype there has been significant interest in understanding their potential roles in neoplasia. Indeed, numerous studies indicate an oncogenic function for ID1, ID2 and ID3. In contrast, the inhibitor of differentiation 4 (ID4) presents a paradigm shift in context of well-established role of ID1, ID2 and ID3 in development and cancer. Apart from some degree of functional redundancy such as HLH dependent interactions with bHLH protein E2A, many of the functions of ID4 are distinct from ID1, ID2 and ID3: ID4 proteins a) regulate distinct developmental processes and tissue expression in the adult, b) promote stem cell survival, differentiation and/or timing of differentiation, c) epigenetic inactivation/loss of expression in several advanced stage cancers and d) increased expression in some cancers such as those arising in the breast and ovary. Thus, in spite of sharing the conserved HLH domain, ID4 defies the established model of ID protein function and expression. The underlying molecular mechanism responsible for the unique role of ID4 as compared to other ID proteins still remains largely un-explored. This review will focus on the current understanding of ID4 in context of development and cancer.


Assuntos
Crescimento e Desenvolvimento/genética , Proteínas Inibidoras de Diferenciação/fisiologia , Neoplasias/genética , Adulto , Sequência de Aminoácidos , Animais , Diferenciação Celular , Humanos , Proteínas Inibidoras de Diferenciação/química , Proteínas Inibidoras de Diferenciação/classificação , Camundongos , Camundongos Knockout , Dados de Sequência Molecular , Neoplasias/patologia , Filogenia , Homologia de Sequência
7.
Curr Top Dev Biol ; 110: 189-216, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25248477

RESUMO

The family of inhibitor of differentiation (Id) proteins is a group of evolutionarily conserved molecules, which play important regulatory roles in organisms ranging from Drosophila to humans. Id proteins are small polypeptides harboring a helix-loop-helix (HLH) motif, which are best known to mediate dimerization with other basic HLH proteins, primarily E proteins. Because Id proteins do not possess the basic amino acids adjacent to the HLH motif necessary for DNA binding, Id proteins inhibit the function of E protein homodimers, as well as heterodimers between E proteins and tissue-specific bHLH proteins. However, Id proteins have also been shown to have E protein-independent functions. The Id genes are broadly but differentially expressed in a variety of cell types. Transcription of the Id genes is controlled by transcription factors such as C/EBPß and Egr as well as by signaling pathways triggered by different stimuli, which include bone morphogenic proteins, cytokines, and ligands of T cell receptors. In general, Id proteins are capable of inhibiting the differentiation of progenitors of different cell types, promoting cell-cycle progression, delaying cellular senescence, and facilitating cell migration. These properties of Id proteins enable them to play significant roles in stem cell maintenance, vasculogenesis, tumorigenesis and metastasis, the development of the immune system, and energy metabolism. In this review, we intend to highlight the current understanding of the function of Id proteins and discuss gaps in our knowledge about the mechanisms whereby Id proteins exert their diverse effects in multiple cellular processes.


Assuntos
Proteínas Inibidoras de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/metabolismo , Adipogenia/fisiologia , Sequência de Aminoácidos , Animais , Regulação da Expressão Gênica , Humanos , Sistema Imunitário/metabolismo , Proteína 1 Inibidora de Diferenciação/química , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo , Proteínas Inibidoras de Diferenciação/química , Dados de Sequência Molecular , Neoplasias/metabolismo , Células-Tronco/fisiologia
8.
PLoS One ; 7(10): e48591, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23119064

RESUMO

Inhibitors of DNA binding and differentiation (ID) proteins, a dominant-negative group of helix-loop-helix (HLH) transcription regulators, are well-characterized key players in cellular fate determination during development in mammals as well as Drosophila. Although not oncogenes themselves, their upregulation by various oncogenic proteins (such as Ras, Myc) and their inhibitory effects on cell cycle proteins (such as pRb) hint at their possible roles in tumorigenesis. Furthermore, their potency as inhibitors of cellular differentiation, through their heterodimerization with subsequent inactivation of the ubiquitous E proteins, suggest possible novel roles in engineering induced pluripotent stem cells (iPSCs). We present the high-resolution 2.1Å crystal structure of ID2 (HLH domain), coupled with novel biochemical insights in the presence of a divalent ion, possibly calcium (Ca2+), in the loop of ID proteins, which appear to be crucial for the structure and activity of ID proteins. These new insights will pave the way for new rational drug designs, in addition to current synthetic peptide options, against this potent player in tumorigenesis as well as more efficient ways for stem cells reprogramming.


Assuntos
Cátions Bivalentes/química , Proteína 2 Inibidora de Diferenciação/química , Proteínas Inibidoras de Diferenciação/química , Proteínas de Neoplasias/química , Multimerização Proteica , Estrutura Terciária de Proteína , Sequência de Aminoácidos , Aminoácidos/química , Aminoácidos/genética , Aminoácidos/metabolismo , Sítios de Ligação/genética , Cálcio/química , Cálcio/metabolismo , Cátions Bivalentes/metabolismo , Cristalografia por Raios X , Ensaio de Desvio de Mobilidade Eletroforética , Escherichia coli/genética , Humanos , Proteína 2 Inibidora de Diferenciação/genética , Proteína 2 Inibidora de Diferenciação/metabolismo , Proteínas Inibidoras de Diferenciação/genética , Proteínas Inibidoras de Diferenciação/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Mutação , Proteína MyoD/química , Proteína MyoD/genética , Proteína MyoD/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Ligação Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Fator 3 de Transcrição/química , Fator 3 de Transcrição/genética , Fator 3 de Transcrição/metabolismo
9.
Oncogene ; 28(17): 1881-91, 2009 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-19330020

RESUMO

Inhibitor of DNA-binding (Id) proteins prevent cell differentiation, promote growth and sustain tumour development. They do so by binding to E proteins and other transcription factors through the helix-loop-helix (HLH) domain, and inhibiting transcription. This makes HLH-mediated Id protein interactions an appealing therapeutic target. We have used the dominant interfering HLH dimerization mutant 13I to model the impact of Id inhibition in two human neuroblastoma cell lines: LA-N-5, similar to immature neuroblasts, and SH-EP, resembling more immature precursor cells. We have validated 13I as an Id inhibitor by showing that it selectively binds to Ids, impairs complex formation with RB, and relieves repression of E protein-activated transcription. Id inactivation by 13I enhances LA-N-5 neural features and causes SH-EP cells to acquire neuronal morphology, express neuronal proteins such as N-CAM and NF-160, proliferate more slowly, and become responsive to retinoic acid. Concomitantly, 13I augments the cell-cycle inhibitor p27(Kip1) and reduces the angiogenic factor vascular endothelial growth factor. These effects are Id specific, being counteracted by Id overexpression. Furthermore, 13I strongly impairs tumorigenic properties in agar colony formation and cell invasion assays. Targeting Id dimerization may therefore be effective for triggering differentiation and restraining neuroblastoma cell tumorigenicity.


Assuntos
Diferenciação Celular/fisiologia , Sequências Hélice-Alça-Hélice/fisiologia , Proteínas Inibidoras de Diferenciação/metabolismo , Western Blotting , Diferenciação Celular/genética , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Forma Celular/genética , Forma Celular/fisiologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27 , Dimerização , Imunofluorescência , Regulação Neoplásica da Expressão Gênica , Sequências Hélice-Alça-Hélice/genética , Humanos , Proteína 1 Inibidora de Diferenciação/genética , Proteína 1 Inibidora de Diferenciação/metabolismo , Proteína 2 Inibidora de Diferenciação/genética , Proteína 2 Inibidora de Diferenciação/metabolismo , Proteínas Inibidoras de Diferenciação/química , Proteínas Inibidoras de Diferenciação/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Mutação , Moléculas de Adesão de Célula Nervosa/metabolismo , Proteínas de Neurofilamentos/metabolismo , Ligação Proteica , Proteína do Retinoblastoma/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Tretinoína/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Cell Mol Biol Lett ; 14(2): 273-87, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19096764

RESUMO

Acheron, a Lupus antigen ortholog, was identified as a novel death-associated transcript from the intersegmental muscles of the moth Manduca sexta. Acheron is phylogenetically-conserved and represents a new sub-family of Lupus antigen proteins. Acheron is expressed predominantly in neurons and muscle in vertebrates, and regulates several developmental events including myogenesis, neurogenesis and possibly metastasis. Using Acheron as bait, we performed a yeast two-hybrid screen with a mouse embryo cDNA library and identified CASK-C, a novel CASK/Lin-2 isoform, as an Acheron binding partner. Acheron and CASK-C bind via the C-terminus of Acheron and the CaMKII-like domain of CASK-C. Co-immunoprecipitation assays verify this interaction and demonstrate that Acheron also forms a complex with all members of the Id (inhibitor of differentiation) proteins. Taken together, these data suggest a mechanism by which Acheron may regulate development and pathology.


Assuntos
Autoantígenos/metabolismo , Guanilato Quinases/metabolismo , Proteínas Inibidoras de Diferenciação/metabolismo , Ribonucleoproteínas/metabolismo , Sequência de Aminoácidos , Animais , Guanilato Quinases/química , Humanos , Proteínas Inibidoras de Diferenciação/química , Proteínas de Insetos/metabolismo , Dados de Sequência Molecular , Mariposas/química , Estrutura Terciária de Proteína , Alinhamento de Sequência , Técnicas do Sistema de Duplo-Híbrido , Antígeno SS-B
11.
J Mol Recognit ; 21(2): 79-88, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18383104

RESUMO

Synthetic agents specifically interacting with a protein interface are important not only for the better understanding of protein dimer or complex formation but also for medical applications. Here we describe the recognition of the helix-loop-helix (HLH) dimerization domain of the Id proteins by an artificial luminescent receptor containing two binding sites for a Lewis acid and a Lewis base, respectively. The Id proteins are inhibitors of bHLH transcription factors and play key roles during development of cancer. We show that a receptor/Id-HLH-domain complex was formed cooperatively (K(0.5) approximately 2 microM under physiological conditions) and with moderate specificity, as compared to the related MyoD and Max HLH domains. Accordingly, a preferred receptor binding motif, CYSR(K), was identified within the Id HLH domains. These results are promising and may be exploited to design highly selective synthetic receptors for the Id HLH domain.


Assuntos
Sequências Hélice-Alça-Hélice , Proteínas Inibidoras de Diferenciação/química , Proteínas Inibidoras de Diferenciação/metabolismo , Metais/metabolismo , Sequência de Aminoácidos , Dicroísmo Circular , Fluorescência , Luminescência , Dados de Sequência Molecular , Peptídeos/química , Ligação Proteica , Estrutura Terciária de Proteína , Titulometria
12.
Mol Biol Cell ; 19(5): 2113-26, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18287524

RESUMO

Id proteins play important roles in osteogenic differentiation; however, the molecular mechanism remains unknown. In this study, we established that inhibitor of differentiation (Id) proteins, including Id1, Id2, and Id3, associate with core binding factor alpha-1 (Cbfa1) to cause diminished transcription of the alkaline phosphatase (ALP) and osteocalcin (OCL) gene, leading to less ALP activity and osteocalcin (OCL) production. Id acts by inhibiting the sequence-specific binding of Cbfa1 to DNA and by decreasing the expression of Cbfa1 in cells undergoing osteogenic differentiation. p204, an interferon-inducible protein that interacts with both Cbfa1 and Id2, overcame the Id2-mediated inhibition of Cbfa1-induced ALP activity and OCL production. We show that 1) p204 disturbed the binding of Id2 to Cbfa1 and enabled Cbfa1 to bind to the promoters of its target genes and 2) that p204 promoted the translocation from nucleus to the cytoplasm and accelerated the degradation of Id2 by ubiquitin-proteasome pathway during osteogenesis. Nucleus export signal (NES) of p204 is required for the p204-enhanced cytoplasmic translocation and degradation of Id2, because a p204 mutant lacking NES lost these activities. Together, Cbfa1, p204, and Id proteins form a regulatory circuit and act in concert to regulate osteoblast differentiation.


Assuntos
Diferenciação Celular , Subunidades alfa de Fatores de Ligação ao Core/metabolismo , Sequências Hélice-Alça-Hélice , Proteínas Inibidoras de Diferenciação/química , Proteínas Inibidoras de Diferenciação/metabolismo , Proteínas Nucleares/metabolismo , Osteogênese , Fosfoproteínas/metabolismo , Fosfatase Alcalina/metabolismo , Sequência de Aminoácidos , Animais , Proteína Morfogenética Óssea 2 , Proteínas Morfogenéticas Ósseas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Subunidades alfa de Fatores de Ligação ao Core/química , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Sinais de Exportação Nuclear , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Regiões Promotoras Genéticas/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Fator de Crescimento Transformador beta/farmacologia , Ubiquitina/metabolismo
15.
Biopolymers ; 80(6): 762-74, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15880794

RESUMO

Id proteins are dominant negative regulators of the helix-loop-helix (HLH) transcription factors and are important during development, especially by preventing cell differentiation while inducing cell proliferation. In contrast, they are poorly expressed in healthy adults but are found in several tumor types. The Id HLH motif is responsible for the inhibitory activity, whereas not much is known about the role of the N- and C-termini. In the presented work, synthetic peptides reproducing the HLH, the N-terminal region, and the C-terminal region of the Id proteins were characterized by CD. The four HLH sequences built highly stable helical conformations, whereas the N- and C-termini were unstructured, with the exception of an alanine-rich fragment preceding the Id4 HLH motif. Deletion of the loop connecting the two helices led to helix destabilization for all four Id HLH peptides. In addition, modifications of the amino acid composition within the hydrophobic face of the helices of the Id1 HLH peptide induced conformational changes, mostly associated with loss of helix content. Moreover, a fragment containing the helix-2 and the C-terminus of the Id1 protein did not show any helical character. Therefore, both the helix propensity and stability of the HLH domain were shown to be strongly dependent on favorable interhelical contacts. In contrast, it is suggested that the regions beyond this domain could rather play a destabilizing role, for example, by increasing the flexibility of the folded protein.


Assuntos
Diferenciação Celular , Sequências Hélice-Alça-Hélice , Peptídeos/química , Peptídeos/síntese química , Fatores de Transcrição/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Substituição de Aminoácidos , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Sequência Conservada , Dimerização , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Interações Hidrofóbicas e Hidrofílicas , Proteína 1 Inibidora de Diferenciação/síntese química , Proteína 1 Inibidora de Diferenciação/química , Proteína 1 Inibidora de Diferenciação/genética , Proteína 2 Inibidora de Diferenciação/síntese química , Proteína 2 Inibidora de Diferenciação/química , Proteínas Inibidoras de Diferenciação/síntese química , Proteínas Inibidoras de Diferenciação/química , Espectrometria de Massas , Dados de Sequência Molecular , Peso Molecular , Peptídeos/genética , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , Deleção de Sequência , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
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