The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

Hmga1  -  high mobility group AT-hook 1

Mus musculus

Synonyms: AL023995, HMG-I(Y), HMGI(Y), HMGY, High mobility group AT-hook protein 1, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of Hmga1

  • Haploinsufficiency of the Hmga1 gene causes cardiac hypertrophy and myelo-lymphoproliferative disorders in mice [1].
  • Elevated expression of the three high-mobility group I (HMGI) proteins (HMGI, HMGY, and HMGI-C) has previously been correlated with the presence of a highly malignant phenotype in epithelial and fibroblastic rat thyroid cells and in experimental thyroid, lung, mammary, and skin carcinomas [2].
  • The primary structure of the Lewis lung carcinoma protein HMGY belonging to the nuclear group of proteins HMGI (high mobility group I) was determined using electrospray and fast atom bombardment mass spectrometry [3].
  • Recently, application of such a research strategy on translocations in uterine leiomyoma involving either chromosome 12q13-15 or 6p21 has led to the discovery that two members of the high-mobility group (HMG) protein gene family, HMGIC and HMGIY, are frequently rearranged in such tumors [4].
 

High impact information on Hmga1

  • Loss of Hmga1 expression, induced in mice by disrupting the Hmga1 gene, considerably decreased insulin receptor expression in the major targets of insulin action, largely impaired insulin signaling and severely reduced insulin secretion, causing a phenotype characteristic of human type 2 diabetes [5].
  • Hmgi-c and another Hmgi family member, Hmgi(gamma) (ref. 10), were found to be expressed predominantly during embryogenesis [6].
  • Both heterozygous and homozygous mice for the Hmga1-null allele show cardiac hypertrophy due to the direct role of HMGA1 on cardiomyocytic cell growth regulation [1].
  • Moreover, the two high performance liquid chromatography-purified forms Y1 and Y2 of the protein HMGY were shown to differ at the level of serine phosphorylation, since they contain three phosphate and two phosphate groups, respectively, in the C-terminal region [3].
  • The murine Hmgi-c gene, a member of the Hmgi gene family, contains five exons encompassing >110 kb of genomic DNA at the pygmy locus on mouse chromosome 10 [7].
 

Biological context of Hmga1

  • The Hmga1/T 3T3-L1 cells had higher E2F activity than the wild-type cells, and a deregulated cell cycle [8].
  • Sequencing confirms that an alternative splicing site within exon 3 results in the two protein isoforms: Hmgi and Hmgy [9].
  • Mass spectrometric analysis of the HMGY protein from Lewis lung carcinoma. Identification of phosphorylation sites [3].
  • Genetic linkage analysis of interspecific and intersubspecific backcrosses showed that Hmgi is located in the t-complex region of mouse Chromosome 17 [10].
  • These analyses reveal a remarkable degree of overall sequence conservation in both the protein coding and promoter regions of the murine and human genes, including conservation of the c-Myc binding site that has been demonstrated to regulate murine Hmgiy transcription (Wood et al., 2000. Mol. Cell. Biol. 20, 5490-5502) [11].
 

Anatomical context of Hmga1

  • We have found that expression of the truncated Hmga1 gene (Hmga1/T) dramatically increases 3T3-L1 cell growth without blocking adipocytic differentiation [8].
  • Therefore, our results indicate that one intact Hmga1 allele was not sufficient for germ-line transmission of the ES cells [12].
  • While the Hmga1(+/-) ES cells were shown to contribute to the formation of the epididymides, they did not significantly contribute to the testes of chimeric founder mice [12].
  • Here we show that the pygmy phenotype arises from the inactivation of Hmgi-c (ref. 6), a member of the Hmgi family which function as architectural factors in the nuclear scaffold and are critical in the assembly of stereospecific transcriptional complexes [6].
  • In contrast, Hmgiy is expressed also in tissues with no proliferative activity, such as the cortical plate of the telencephalon and the spinal cord at late gestational stages [13].
 

Other interactions of Hmga1

  • The HMGI family consists of three members: HMGI, HMGY and HMGI-C [9].
 

Analytical, diagnostic and therapeutic context of Hmga1

  • Using gel-retardation assay, we demonstrate that two members of the high mobility group I (HMGI) family of nuclear proteins (HMGI-C and HMGY) can bind to a subset of HD target sequences and inhibit HDs from binding to the same sequences [14].

References

  1. Haploinsufficiency of the Hmga1 gene causes cardiac hypertrophy and myelo-lymphoproliferative disorders in mice. Fedele, M., Fidanza, V., Battista, S., Pentimalli, F., Klein-Szanto, A.J., Visone, R., De Martino, I., Curcio, A., Morisco, C., Del Vecchio, L., Baldassarre, G., Arra, C., Viglietto, G., Indolfi, C., Croce, C.M., Fusco, A. Cancer Res. (2006) [Pubmed]
  2. Inhibition of HMGI-C protein synthesis suppresses retrovirally induced neoplastic transformation of rat thyroid cells. Berlingieri, M.T., Manfioletti, G., Santoro, M., Bandiera, A., Visconti, R., Giancotti, V., Fusco, A. Mol. Cell. Biol. (1995) [Pubmed]
  3. Mass spectrometric analysis of the HMGY protein from Lewis lung carcinoma. Identification of phosphorylation sites. Ferranti, P., Malorni, A., Marino, G., Pucci, P., Goodwin, G.H., Manfioletti, G., Giancotti, V. J. Biol. Chem. (1992) [Pubmed]
  4. Genetic basis of uterine leiomyoma: involvement of high mobility group protein genes. Van de Ven, W.J. Eur. J. Obstet. Gynecol. Reprod. Biol. (1998) [Pubmed]
  5. Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice. Foti, D., Chiefari, E., Fedele, M., Iuliano, R., Brunetti, L., Paonessa, F., Manfioletti, G., Barbetti, F., Brunetti, A., Croce, C.M., Fusco, A., Brunetti, A. Nat. Med. (2005) [Pubmed]
  6. Mutation responsible for the mouse pygmy phenotype in the developmentally regulated factor HMGI-C. Zhou, X., Benson, K.F., Ashar, H.R., Chada, K. Nature (1995) [Pubmed]
  7. Genomic structure and expression of the murine Hmgi-c gene. Zhou, X., Benson, K.F., Przybysz, K., Liu, J., Hou, Y., Cherath, L., Chada, K. Nucleic Acids Res. (1996) [Pubmed]
  8. A truncated HMGA1 gene induces proliferation of the 3T3-L1 pre-adipocytic cells: a model of human lipomas. Pierantoni, G.M., Battista, S., Pentimalli, F., Fedele, M., Visone, R., Federico, A., Santoro, M., Viglietto, G., Fusco, A. Carcinogenesis (2003) [Pubmed]
  9. Genomic structure and expression of the murine Hmgi(y) gene. Liu, J., Schiltz, J.F., Shah, P.C., Benson, K.F., Chada, K.K. Gene (2000) [Pubmed]
  10. Chromosomal localization of the murine gene and two related sequences encoding high-mobility-group I and Y proteins. Johnson, K.R., Cook, S.A., Davisson, M.T. Genomics (1992) [Pubmed]
  11. Sequence and analysis of the murine Hmgiy (Hmga1) gene locus. Pedulla, M.L., Treff, N.R., Resar, L.M., Reeves, R. Gene (2001) [Pubmed]
  12. Hmga1 is required for normal sperm development. Liu, J., Schiltz, J.F., Ashar, H.R., Chada, K.K. Mol. Reprod. Dev. (2003) [Pubmed]
  13. The expression pattern of the Hmgic gene during development. Hirning-Folz, U., Wilda, M., Rippe, V., Bullerdiek, J., Hameister, H. Genes Chromosomes Cancer (1998) [Pubmed]
  14. High mobility group I proteins interfere with the homeodomains binding to DNA. Arlotta, P., Rustighi, A., Mantovani, F., Manfioletti, G., Giancotti, V., Tell, G., Damante, G. J. Biol. Chem. (1997) [Pubmed]
 
WikiGenes - Universities