hmga proteins


Summary: Proteins containing AT-HOOK MOTIFS that are rich in arginine and glycine residues. They bind to the minor grove of AT-rich regions of DNA.

Top Publications

  1. Palmieri D, Valentino T, D Angelo D, De Martino I, Postiglione I, Pacelli R, et al. HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents. Oncogene. 2011;30:3024-35 pubmed publisher
    ..Interestingly, we found that HMGA proteins positively regulate ATM gene expression...
  2. Reeves R, Beckerbauer L. HMGA proteins as therapeutic drug targets. Prog Cell Cycle Res. 2003;5:279-86 pubmed
    ..The HMGA proteins are also frequently associated with various malignancies...
  3. Sarhadi V, Wikman H, Salmenkivi K, Kuosma E, Sioris T, Salo J, et al. Increased expression of high mobility group A proteins in lung cancer. J Pathol. 2006;209:206-12 pubmed
    ..As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, ..
  4. Liu L, Ding H, Wang H, Xu Y, Cui G, Wang P, et al. Polymorphism of HMGA1 is associated with increased risk of type 2 diabetes among Chinese individuals. Diabetologia. 2012;55:1685-8 pubmed publisher
    ..0%. HMGA1 is an important susceptibility locus that confers a high cross-race risk of the development of type 2 diabetes. ..
  5. Martinez Hoyos J, Fedele M, Battista S, Pentimalli F, Kruhoffer M, Arra C, et al. Identification of the genes up- and down-regulated by the high mobility group A1 (HMGA1) proteins: tissue specificity of the HMGA1-dependent gene regulation. Cancer Res. 2004;64:5728-35 pubmed
  6. Reeves R. Nuclear functions of the HMG proteins. Biochim Biophys Acta. 2010;1799:3-14 pubmed publisher
    ..The biological implications of having three architectural transcription factor families with complementary, but partially overlapping, nuclear functions are discussed. ..
  7. Liau S, Ashley S, Whang E. Lentivirus-mediated RNA interference of HMGA1 promotes chemosensitivity to gemcitabine in pancreatic adenocarcinoma. J Gastrointest Surg. 2006;10:1254-62; discussion 1263 pubmed
    ..Lentivirus-mediated RNA interference of HMGA1 promoted chemosensitivity to gemcitabine in pancreatic adenocarcinoma. HMGA1 may represent a novel therapeutic target in pancreatic cancer. ..
  8. Kim K, Lee J, Shin H, Choi B, Lee C, Kim J, et al. Association of melanocortin 4 receptor (MC4R) and high mobility group AT-hook 1 (HMGA1) polymorphisms with pig growth and fat deposition traits. Anim Genet. 2006;37:419-21 pubmed
    ..Therefore, utilization of polymorphisms in both MC4R and HMGA1 for marker-assisted selection could result in an economic benefit to the pig industry. ..
  9. Hock R, Furusawa T, Ueda T, Bustin M. HMG chromosomal proteins in development and disease. Trends Cell Biol. 2007;17:72-9 pubmed
    ..Here, we focus on the biological function of HMG proteins and highlight their possible roles in cellular differentiation and in the etiology of various diseases. ..

More Information


  1. Hui P, Li N, Johnson C, De Wever I, Sciot R, Manfioletti G, et al. HMGA proteins in malignant peripheral nerve sheath tumor and synovial sarcoma: preferential expression of HMGA2 in malignant peripheral nerve sheath tumor. Mod Pathol. 2005;18:1519-26 pubmed
    ..In summary, expression of HMGA2 is a feature of MPNST but not of synovial sarcoma and immunohistochemical staining of HMGA2 may be a useful marker to separate malignant peripheral nerve sheath tumor from synovial sarcoma. ..
  2. Kishi Y, Fujii Y, Hirabayashi Y, Gotoh Y. HMGA regulates the global chromatin state and neurogenic potential in neocortical precursor cells. Nat Neurosci. 2012;15:1127-33 pubmed
    ..Knockdown of HMGA proteins in early-stage NPCs reduced their neurogenic potential...
  3. Sgarra R, Zammitti S, Lo Sardo A, Maurizio E, Arnoldo L, Pegoraro S, et al. HMGA molecular network: From transcriptional regulation to chromatin remodeling. Biochim Biophys Acta. 2010;1799:37-47 pubmed publisher
    ..The HMGA proteins are chromatin architectural factors which constitute critical hubs in these networks...
  4. Kim K, Thomsen H, Bastiaansen J, Nguyen N, Dekkers J, Plastow G, et al. Investigation of obesity candidate genes on porcine fat deposition quantitative trait loci regions. Obes Res. 2004;12:1981-94 pubmed
  5. Cleynen I, Van de Ven W. The HMGA proteins: a myriad of functions (Review). Int J Oncol. 2008;32:289-305 pubmed
    ..b>HMGA proteins are characterized by three DNA-binding domains, called AT-hooks, and an acidic carboxy-terminal tail...
  6. Zhang Q, Wang Y. HMG modifications and nuclear function. Biochim Biophys Acta. 2010;1799:28-36 pubmed publisher
    ..In this review, we focus on the chemical modifications of mammalian HMG proteins and highlight their roles in nuclear functions. ..
  7. Chang Z, Yang L, Wang W, Peng J, Huang G, Tao Y, et al. Determination of high mobility group A1 (HMGA1) expression in hepatocellular carcinoma: a potential prognostic marker. Dig Dis Sci. 2005;50:1764-70 pubmed
    ..05). Our findings indicate that HMGA1 may be involved in the carcinogenesis and invasiveness of HCC and the determination of HMGA1 can be of great value in predicting the prognosis of patients with HCC. ..
  8. Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer. 2007;7:899-910 pubmed
    ..Here, we focus on the role of the HMGA proteins in human neoplastic diseases, the mechanisms by which they contribute to carcinogenesis, and therapeutic ..
  9. Benecke A, Eilebrecht S. RNA-Mediated Regulation of HMGA1 Function. Biomolecules. 2015;5:943-57 pubmed
    ..In this review, we discuss the structure and function of HMGA1-RNA complexes during transcription and epigenomic regulation and their implications in HMGA1-related diseases. ..
  10. Mu G, Liu H, Zhou F, Xu X, Jiang H, Wang Y, et al. Correlation of overexpression of HMGA1 and HMGA2 with poor tumor differentiation, invasion, and proliferation associated with let-7 down-regulation in retinoblastomas. Hum Pathol. 2010;41:493-502 pubmed publisher
    ..04; r = -0.392, P = .007, respectively). Our findings imply that the overexpressions of high-mobility group A1, high-mobility group A2, and down-regulation of let-7 may be associated with tumorigenesis and progression of retinoblastomas. ..
  11. Wang E, Qian Z, Rahman M, Yoshimoto K, Yamada S, Kudo E, et al. Increased expression of HMGA1 correlates with tumour invasiveness and proliferation in human pituitary adenomas. Histopathology. 2010;56:501-9 pubmed publisher
    ..368, P < 0.0002). These findings suggest that HMGA1 up-regulation has an important oncogenic role in pituitary tumorigenesis, as well as being a novel molecular marker of tumour proliferation and invasiveness. ..
  12. Palmieri D, D Angelo D, Valentino T, De Martino I, Ferraro A, Wierinckx A, et al. Downregulation of HMGA-targeting microRNAs has a critical role in human pituitary tumorigenesis. Oncogene. 2012;31:3857-65 pubmed publisher
    ..Therefore, these results indicate that the downregulation of the miRNAs able to target the HMGA genes could contribute to increase HMGA protein levels in human pituitary adenomas, and then to pituitary tumorigenesis. ..
  13. Maasch C, Vater A, Buchner K, Purschke W, Eulberg D, Vonhoff S, et al. Polyetheylenimine-polyplexes of Spiegelmer NOX-A50 directed against intracellular high mobility group protein A1 (HMGA1) reduce tumor growth in vivo. J Biol Chem. 2010;285:40012-8 pubmed publisher
    ..Our results demonstrate that intracellular targets can be successfully addressed with a Spiegelmer using polyethylenimine-based delivery and underline the importance of HMGA1 as a therapeutic target in pancreatic cancer. ..
  14. Launholt D, Merkle T, Houben A, Schulz A, Grasser K. Arabidopsis chromatin-associated HMGA and HMGB use different nuclear targeting signals and display highly dynamic localization within the nucleus. Plant Cell. 2006;18:2904-18 pubmed
    ..The HMGA proteins are characterized by the presence of four AT-hook DNA binding motifs, and the HMGB proteins contain an HMG box ..
  15. Reisdorf Cren M, Carrayol E, Terc Laforgue T, Hirel B. A novel HMG A-like protein binds differentially to the AT-rich regions located in the far distal and proximal parts of a soybean glutamine synthetase gene (GS15) promoter. Plant Cell Physiol. 2002;43:1006-16 pubmed
    ..This result suggests that AT-1SNBP may be an architectural protein involved in maintaining the spatial conformation of the GS15 promoter, thus facilitating the interaction between the distal and proximal regulatory elements...
  16. Kubo T, Matsui Y, Goto T, Yukata K, Endo K, Sato R, et al. MRI characteristics of parosteal lipomas associated with the HMGA2-LPP fusion gene. Anticancer Res. 2006;26:2253-7 pubmed
    ..Since the HMGA2-LPP fusion transcripts are exclusively detectable in benign mesenchymal tumors, testing HMGA2-LPP expression may be useful for differential diagnosis in cases of radiologically-suspected well-differentiated liposarcomas. ..
  17. Maruyama T, Asada H, Ono M, Arase T, Yoshimura Y. [Uterine leiomyoma]. Nihon Rinsho. 2006;Suppl 2:477-84 pubmed
  18. Yang Z, Yang J, Liu W, Wu L, Xing L, Wang Y, et al. T2D@ZJU: a knowledgebase integrating heterogeneous connections associated with type 2 diabetes mellitus. Database (Oxford). 2013;2013:bat052 pubmed publisher
    ..The functionality of T2D@ZJU is shown by means of several case studies. Database URL: ..
  19. Ishikawa F, Kaneko E, Sugimoto T, Ishijima T, Wakamatsu M, Yuasa A, et al. A mitochondrial thioredoxin-sensitive mechanism regulates TGF-?-mediated gene expression associated with epithelial-mesenchymal transition. Biochem Biophys Res Commun. 2014;443:821-7 pubmed publisher
  20. Liau S, Jazag A, Ito K, Whang E. Overexpression of HMGA1 promotes anoikis resistance and constitutive Akt activation in pancreatic adenocarcinoma cells. Br J Cancer. 2007;96:993-1000 pubmed
    ..Given the putative associations between anoikis resistance and metastatic potential, HMGA1 represents a potential therapeutic target in pancreatic adenocarcinoma. ..
  21. Brannon K, Million Passe C, White C, Bade N, King M, Quirk C. Expression of the high mobility group A family member p8 is essential to maintaining tumorigenic potential by promoting cell cycle dysregulation in LbetaT2 cells. Cancer Lett. 2007;254:146-55 pubmed
    ..These phenotypic changes correspond to altered cell cycle regulation at the G(1)-to-S transition that may be due to p8-mediated changes in expression of the Cip/Kip family members of cell cycle inhibitors, p21, p27, and p57. ..
  22. von Ahsen I, Rogalla P, Bullerdiek J. Expression patterns of the LPP-HMGA2 fusion transcript in pulmonary chondroid hamartomas with t(3;12)(q27 approximately 28;q14 approximately 15). Cancer Genet Cytogenet. 2005;163:68-70 pubmed
    ..Thus, based on this one finding, a role of LPP-HMGA2 in PCH should be considered. ..
  23. Narita M, Narita M, Krizhanovsky V, Nũnez S, Chicas A, Hearn S, et al. A novel role for high-mobility group a proteins in cellular senescence and heterochromatin formation. Cell. 2006;126:503-14 pubmed
    ..b>HMGA proteins cooperate with the p16(INK4a) tumor suppressor to promote SAHF formation and proliferative arrest and ..
  24. Grant M, Baron R, Macias A, Layne M, Perrella M, Rigby A. Netropsin improves survival from endotoxaemia by disrupting HMGA1 binding to the NOS2 promoter. Biochem J. 2009;418:103-12 pubmed publisher
  25. Abraham J, Brooks P. Divergent effects of oxidatively induced modification to the C8 of 2'-deoxyadenosine on transcription factor binding: 8,5'(S)-cyclo-2'-deoxyadenosine inhibits the binding of multiple sequence specific transcription factors, while 8-oxo-2'-deoxyadenos. Environ Mol Mutagen. 2011;52:287-95 pubmed publisher
    ..The cyclo-dAdo lesion, in contrast, distorted the DNA structure, providing an explanation for the inhibition of NF-kappaB binding. ..
  26. Elías Arnanz M, Padmanabhan S, Murillo F. The regulatory action of the myxobacterial CarD/CarG complex: a bacterial enhanceosome?. FEMS Microbiol Rev. 2010;34:764-78 pubmed publisher
  27. Cao Y, Huang P, Sun X, Ma J, Jin Z, Cheng H, et al. Silencing of high mobility group A1 enhances gemcitabine chemosensitivity of lung adenocarcinoma cells. Chin Med J (Engl). 2011;124:1061-8 pubmed
    ..The mechanism may be associated with the PI-3K/Akt signal pathway. HMGA1 may represent a novel therapeutic target in lung cancer. ..
  28. Chiefari E, Iiritano S, Paonessa F, Le Pera I, Arcidiacono B, Filocamo M, et al. Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes. Nat Commun. 2010;1:40 pubmed publisher
    ..These data provide evidence for a regulatory role of an expressed pseudogene in humans and establishes a novel mechanistic linkage between pseudogene HMGA1-p expression and type 2 diabetes mellitus. ..
  29. Akhter M, Luthra K, Rajeswari M. Molecular aspects on adriamycin interaction with hmga1 regulatory region and its inhibitory effect on HMGA1 expression in human cervical cancer. J Biomol Struct Dyn. 2016;34:877-91 pubmed publisher
    ..Therefore, hmga1 in general and particularly the regulatory region is a promising target for therapeutic strategy in combating cancer. ..
  30. Reeves R. HMGA proteins: isolation, biochemical modifications, and nucleosome interactions. Methods Enzymol. 2004;375:297-322 pubmed
  31. Li N, McNiff J, Hui P, Manfioletti G, Tallini G. Differential expression of HMGA1 and HMGA2 in dermatofibroma and dermatofibrosarcoma protuberans: potential diagnostic applications, and comparison with histologic findings, CD34, and factor XIIIa immunoreactivity. Am J Dermatopathol. 2004;26:267-72 pubmed
    ..001). We conclude that HMGA1 and HMGA2 expression can be used to distinguish DF from DFSP with a degree of accuracy that is fully equivalent to that of Factor XIIIa and CD34. ..
  32. Diana F, Di Bernardo J, Sgarra R, Tessari M, Rustighi A, Fusco A, et al. Differential HMGA expression and post-translational modifications in prostatic tumor cells. Int J Oncol. 2005;26:515-20 pubmed
    ..Here we investigate the expression and post-translational modifications (PTMs) of HMGA proteins (HMGA1a, HMGA1b and HMGA2) in the rat prostatic cancer Dunning model (G, AT-1, and MAT-Ly-Lu cell lines)...
  33. Lecanidou R, Papantonis A. Silkmoth chorion gene regulation revisited: promoter architecture as a key player. Insect Mol Biol. 2010;19:141-51 pubmed publisher
    ..In this review we present a parsimonious model that adequately describes regulation of transcription across all temporally regulated chorion genes, and propose a role for promoter architecture. ..
  34. Xu M, Sharma P, Pan S, Malik S, Roeder R, Martinez E. Core promoter-selective function of HMGA1 and Mediator in Initiator-dependent transcription. Genes Dev. 2011;25:2513-24 pubmed publisher
    ..Our results suggest a core promoter-specific regulation of Mediator and the basal transcription machinery by HMGA1. ..
  35. D Angelo D, Borbone E, Palmieri D, Uboldi S, Esposito F, Frapolli R, et al. The impairment of the High Mobility Group A (HMGA) protein function contributes to the anticancer activity of trabectedin. Eur J Cancer. 2013;49:1142-51 pubmed publisher
    ..Then, we have shown that trabectedin treatment displaces HMGA proteins from the HMGA-responsive promoters, including ATM promoter, impairing their transcriptional activity...
  36. Medeiros F, Wang X, Araujo A, Erickson Johnson M, Lima J, Meuter A, et al. HMGA gene rearrangement is a recurrent somatic alteration in polypoid endometriosis. Hum Pathol. 2012;43:1243-8 pubmed publisher
    ..These findings suggest that HMGA rearrangements likely contribute to the pathogenesis of endometriosis. However, additional studies are needed to better define the biologic role of this genetic alteration. ..
  37. Pierantoni G, Agosti V, Fedele M, Bond H, Caliendo I, Chiappetta G, et al. High-mobility group A1 proteins are overexpressed in human leukaemias. Biochem J. 2003;372:145-50 pubmed
    ..g. lipomas, lung hamartomas and uterine leiomiomas. HMGA proteins have been implicated in the control of cell growth and differentiation of the pre-adipocytic cell line 3T3-L1...
  38. Watanabe M, Sheriff S, Lewis K, Tinch S, Cho J, Balasubramaniam A, et al. HMGA-targeted phosphorothioate DNA aptamers increase sensitivity to gemcitabine chemotherapy in human pancreatic cancer cell lines. Cancer Lett. 2012;315:18-27 pubmed publisher
    ..The data indicate the potential use of HMGA targeted DNA aptamers to enhance chemotherapy efficacy in pancreatic cancer treatment. ..
  39. Fonfría Subirós E, Acosta Reyes F, Saperas N, Pous J, Subirana J, Campos J. Crystal structure of a complex of DNA with one AT-hook of HMGA1. PLoS ONE. 2012;7:e37120 pubmed publisher
    ..The structure presents analogies and significant differences with previous NMR studies: the AT-hook forms hydrogen bonds between main-chain NH groups and thymines in the minor groove, DNA is bent and the minor groove is widened. ..
  40. Chiefari E, Tanyolac S, Paonessa F, Pullinger C, Capula C, Iiritano S, et al. Functional variants of the HMGA1 gene and type 2 diabetes mellitus. JAMA. 2011;305:903-12 pubmed publisher
    ..Compared with healthy controls, the presence of functional HMGA1 gene variants in individuals of white European ancestry was associated with type 2 DM. ..
  41. Medeiros F, Araujo A, Erickson Johnson M, Kashyap P, Dal Cin P, Nucci M, et al. HMGA1 and HMGA2 rearrangements in mass-forming endometriosis. Genes Chromosomes Cancer. 2010;49:630-4 pubmed publisher
    ..The present findings support the concept that endometriosis is clonal and that rearrangement of HMGA genes likely contributes to its pathogenesis. ..
  42. Fedele M, Fusco A. Role of the high mobility group A proteins in the regulation of pituitary cell cycle. J Mol Endocrinol. 2010;44:309-18 pubmed publisher
    ..Here, we first review the role of the cell cycle in pituitary tumorigenesis, as witnessed by human pathology and transgenic mice; and then, we focus on HMGA proteins and their cell cycle-related role in pituitary tumorigenesis.
  43. Chau K, Keane Myers A, Fedele M, Ikeda Y, Creusot R, Menozzi L, et al. IFN-gamma gene expression is controlled by the architectural transcription factor HMGA1. Int Immunol. 2005;17:297-306 pubmed
    ..In vitro binding assays further demonstrated a specific interaction of HMGA1 to defined regions of the IFNG gene proximal promoter. ..
  44. Abe N, Watanabe T, Izumisato Y, Suzuki Y, Masaki T, Mori T, et al. High mobility group A1 is expressed in metastatic adenocarcinoma to the liver and intrahepatic cholangiocarcinoma, but not in hepatocellular carcinoma: its potential use in the diagnosis of liver neoplasms. J Gastroenterol. 2003;38:1144-9 pubmed
  45. Strichman Almashanu L, Bustin M, Landsman D. Retroposed copies of the HMG genes: a window to genome dynamics. Genome Res. 2003;13:800-12 pubmed
    ..Finally, because our algorithm included aligning RPC flanking sequences with the corresponding HMG genomic sequence, we were able to identify transcribed regions of HMG genes that were not part of the published mRNA sequences. ..
  46. Matta M, Panagiotidis C. High-mobility group protein A1 binds herpes simplex virus gene regulatory sequences and affects their expression. Arch Virol. 2008;153:1251-62 pubmed publisher
    ..These data indicate that host-cell architectural chromatin proteins could influence the interactions of host-cell and viral transcription factors with the virus DNA regulatory elements and affect HSV-1 gene expression. ..
  47. Dunker A, Cortese M, Romero P, Iakoucheva L, Uversky V. Flexible nets. The roles of intrinsic disorder in protein interaction networks. FEBS J. 2005;272:5129-48 pubmed
    ..An important research direction will be to determine what fraction of protein-protein interaction in regulatory networks relies on intrinsic disorder. ..
  48. Forzati F, Federico A, Pallante P, Fedele M, Fusco A. Tumor suppressor activity of CBX7 in lung carcinogenesis. Cell Cycle. 2012;11:1888-91 pubmed publisher
    ..A similar mechanism is likely involved in human lung carcinogenesis, since cyclin E upregulation associated with the loss of CBX7 expression has been observed in most of the human lung carcinomas analyzed. ..
  49. Sgarra R, Tessari M, Di Bernardo J, Rustighi A, Zago P, Liberatori S, et al. Discovering high mobility group A molecular partners in tumour cells. Proteomics. 2005;5:1494-506 pubmed
    ..Taken together, these experimental data indicate that HMGA proteins are highly connected nodes in the chromatin protein network...
  50. Crombez K, Vanoirbeek E, Van de Ven W, Petit M. Transactivation functions of the tumor-specific HMGA2/LPP fusion protein are augmented by wild-type HMGA2. Mol Cancer Res. 2005;3:63-70 pubmed
    ..These results support the concept that the transactivation functions of the novel HMGA2/LPP transcription factor contribute to lipomagenesis. ..
  51. Battista S, Fedele M, Martinez Hoyos J, Pentimalli F, Pierantoni G, Visone R, et al. High-mobility-group A1 (HMGA1) proteins down-regulate the expression of the recombination activating gene 2 (RAG2). Biochem J. 2005;389:91-7 pubmed
    ..Since RAG2 is necessary for lymphoid cell development, our results suggest a novel mechanism by which HMGA1 might regulate lymphoid differentiation. ..
  52. Boultwood J, Wainscoat J. High-mobility group A (HMGA) genes: from solid to liquid tumours?. Leukemia. 2005;19:195-6 pubmed
  53. Martins V, Busch K, Juraeva D, Blum C, Ludwig C, Rasche V, et al. Cell competition is a tumour suppressor mechanism in the thymus. Nature. 2014;509:465-70 pubmed publisher