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Nhlh1  -  nescient helix loop helix 1

Mus musculus

Synonyms: HEN-1, Helix-loop-helix protein 1, Hen1, NSCL-1, Nescient helix loop helix 1, ...
 
 
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Disease relevance of Nhlh1

  • The pattern of altered heart rhythm observed in basal and experimental conditions (stress and pharmacologically induced) suggests that a deficient parasympathetic tone may contribute to the arrhythmia in the Nhlh1-null mouse [1].
  • To gain further insights into this process, we screened for NSCL target genes using DNA array hybridization and detected necdin, which is deleted in the human Prader-Willi syndrome phenotypically resembling the NSCL-2 mutation [2].
  • The basic helix-loop-helix protein, achaete-scute complex-like 1/achaete-scute homologue 1 (ASH1), is expressed in normal fetal pulmonary neuroendocrine cells and lung cancers with neuroendocrine elements and is suggested to be involved in lung carcinogenesis [3].
  • Validation of differential expression using melanoma tissue microarrays showed that reduced ubiquitin COOH-terminal esterase L1 in primary melanoma is associated with worse outcome and that increased expression of the basic helix-loop-helix protein Twist is associated with worse outcome [4].
  • The helix-loop-helix protein Id inhibits differentiation of murine erythroleukemia cells [5].
 

Psychiatry related information on Nhlh1

 

High impact information on Nhlh1

 

Biological context of Nhlh1

 

Anatomical context of Nhlh1

 

Associations of Nhlh1 with chemical compounds

 

Physical interactions of Nhlh1

 

Regulatory relationships of Nhlh1

 

Other interactions of Nhlh1

  • The nucleotide and predicted protein sequences of Nhlh1 and Nhlh2 are homologous within their bHLH domain where there are only three conservative amino acid differences [7].
  • Nhlh1, a member of the basic helix-loop-helix family of transcription factors, is expressed in the developing neural tube in structures affected by the Lp mutation and has been regionally assigned to the distal part of mouse Chr 1 [26].
  • In this paper, we examine the expression of Nhlh1 transcripts at early embryonic stages (E8.5-E10.5), at the onset of neurogenesis, and compare the pattern of expression with that of Islet-1, a marker of postmitotic neurons [22].
  • We postulate that the Id3 protein is a negative regulator of fat cell formation and presumably acts by preventing an as yet unidentified basic helix-loop-helix protein from activating the program of differentiation [27].
  • Analysis of sensory neurons which strongly express NSCL-1 revealed that the spatiotemporal expression of neuronal differentiation factors, such as NeuroD and SCG-10, was not altered in developing distal and proximal cranial ganglia of mutant mice [28].
 

Analytical, diagnostic and therapeutic context of Nhlh1

  • By in situ hybridization, NSCL-1 mRNA was found in the premigratory zone of the external granule layer (EGL), a structure developmentally analogous to the subependymal zone of the embryonic brain [29].
  • By Northern blot hybridization analysis, the expression levels of Id-1 and NSCL-1 mRNA were developmentally regulated in the cerebellum, with the highest mRNA levels coinciding with the time of maximal granule cell histogenesis [29].
  • Molecular cloning and characterization of a cDNA encoding a novel basic helix-loop-helix protein structurally related to Neuro-D/BHF1 [30].
  • We show that PX-866, a PI3-K inhibitor with selectivity for p110alpha, potentiates the antitumor activity of gefitinib against even large A-549 NSCL xenografts giving complete tumor growth control in the early stages of treatment [31].

References

  1. Predisposition to arrhythmia and autonomic dysfunction in Nhlh1-deficient mice. Cogliati, T., Good, D.J., Haigney, M., Delgado-Romero, P., Eckhaus, M.A., Koch, W.J., Kirsch, I.R. Mol. Cell. Biol. (2002) [Pubmed]
  2. NSCL-1 and NSCL-2 synergistically determine the fate of GnRH-1 neurons and control necdin gene expression. Krüger, M., Ruschke, K., Braun, T. EMBO J. (2004) [Pubmed]
  3. ASH1 gene is a specific therapeutic target for lung cancers with neuroendocrine features. Osada, H., Tatematsu, Y., Yatabe, Y., Horio, Y., Takahashi, T. Cancer Res. (2005) [Pubmed]
  4. Expression profiling reveals novel pathways in the transformation of melanocytes to melanomas. Hoek, K., Rimm, D.L., Williams, K.R., Zhao, H., Ariyan, S., Lin, A., Kluger, H.M., Berger, A.J., Cheng, E., Trombetta, E.S., Wu, T., Niinobe, M., Yoshikawa, K., Hannigan, G.E., Halaban, R. Cancer Res. (2004) [Pubmed]
  5. The helix-loop-helix protein Id inhibits differentiation of murine erythroleukemia cells. Shoji, W., Yamamoto, T., Obinata, M. J. Biol. Chem. (1994) [Pubmed]
  6. Repression of immunoglobulin enhancers by the helix-loop-helix protein Id: implications for B-lymphoid-cell development. Wilson, R.B., Kiledjian, M., Shen, C.P., Benezra, R., Zwollo, P., Dymecki, S.M., Desiderio, S.V., Kadesch, T. Mol. Cell. Biol. (1991) [Pubmed]
  7. Hypogonadism and obesity in mice with a targeted deletion of the Nhlh2 gene. Good, D.J., Porter, F.D., Mahon, K.A., Parlow, A.F., Westphal, H., Kirsch, I.R. Nat. Genet. (1997) [Pubmed]
  8. Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. Lee, J.E., Hollenberg, S.M., Snider, L., Turner, D.L., Lipnick, N., Weintraub, H. Science (1995) [Pubmed]
  9. A CLOCK-less clock. Asher, G., Schibler, U. Trends Cell Biol. (2006) [Pubmed]
  10. Helix-loop-helix proteins and lymphocyte development. Murre, C. Nat. Immunol. (2005) [Pubmed]
  11. E-proteins directly regulate expression of activation-induced deaminase in mature B cells. Sayegh, C.E., Quong, M.W., Agata, Y., Murre, C. Nat. Immunol. (2003) [Pubmed]
  12. Molecular characterization of NSCL, a gene encoding a helix-loop-helix protein expressed in the developing nervous system. Begley, C.G., Lipkowitz, S., Göbel, V., Mahon, K.A., Bertness, V., Green, A.R., Gough, N.M., Kirsch, I.R. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  13. A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development. Wang, S., Sdrulla, A., Johnson, J.E., Yokota, Y., Barres, B.A. Neuron (2001) [Pubmed]
  14. An Id-related helix-loop-helix protein encoded by a growth factor-inducible gene. Christy, B.A., Sanders, L.K., Lau, L.F., Copeland, N.G., Jenkins, N.A., Nathans, D. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  15. Suppression of mammary epithelial cell differentiation by the helix-loop-helix protein Id-1. Desprez, P.Y., Hara, E., Bissell, M.J., Campisi, J. Mol. Cell. Biol. (1995) [Pubmed]
  16. FIGalpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes. Liang, L., Soyal, S.M., Dean, J. Development (1997) [Pubmed]
  17. Efficacy of cytotoxic agents against human tumor xenografts is markedly enhanced by coadministration of ZD1839 (Iressa), an inhibitor of EGFR tyrosine kinase. Sirotnak, F.M., Zakowski, M.F., Miller, V.A., Scher, H.I., Kris, M.G. Clin. Cancer Res. (2000) [Pubmed]
  18. Structural features of the murine gene encoding the RI beta subunit of cAMP-dependent protein kinase. Clegg, C.H., Koeiman, N.R., Jenkins, N.A., Gilbert, D.J., Copeland, N.G., Neubauer, M.G. Mol. Cell. Neurosci. (1994) [Pubmed]
  19. Helix-loop-helix transcription factors regulate Id2 gene promoter activity. Neuman, K., Nornes, H.O., Neuman, T. FEBS Lett. (1995) [Pubmed]
  20. Preclinical antitumor activity of 4'-thio-beta-D-arabinofuranosylcytosine (4'-thio-ara-C). Waud, W.R., Gilbert, K.S., Shepherd, R.V., Montgomery, J.A., Secrist, J.A. Cancer Chemother. Pharmacol. (2003) [Pubmed]
  21. Id-1 promotes proliferation of p53-deficient esophageal cancer cells. Hui, C.M., Cheung, P.Y., Ling, M.T., Tsao, S.W., Wang, X., Wong, Y.C., Cheung, A.L. Int. J. Cancer (2006) [Pubmed]
  22. Sequence and expression analysis of Nhlh1: a basic helix-loop-helix gene implicated in neurogenesis. Murdoch, J.N., Eddleston, J., Leblond-Bourget, N., Stanier, P., Copp, A.J. Dev. Genet. (1999) [Pubmed]
  23. Transcription of the dominant-negative helix-loop-helix protein Id1 is regulated by a protein complex containing the immediate-early response gene Egr-1. Tournay, O., Benezra, R. Mol. Cell. Biol. (1996) [Pubmed]
  24. Expression of bHLH transcription factors NSCL1 and NSCL2 in the mouse olfactory system. Suzuki, Y., Tsuruga, E., Yajima, T., Takeda, M. Chem. Senses (2003) [Pubmed]
  25. Insulin expression in pancreatic islet cells relies on cooperative interactions between the helix loop helix factor E47 and the homeobox factor STF-1. Peers, B., Leonard, J., Sharma, S., Teitelman, G., Montminy, M.R. Mol. Endocrinol. (1994) [Pubmed]
  26. Nhlh1, a basic helix-loop-helix transcription factor, is very tightly linked to the mouse looptail (Lp) mutation. Mullick, A., Groulx, N., Trasler, D., Gros, P. Mamm. Genome (1995) [Pubmed]
  27. Id3 prevents differentiation of preadipose cells. Moldes, M., Lasnier, F., Fève, B., Pairault, J., Djian, P. Mol. Cell. Biol. (1997) [Pubmed]
  28. The neuronal basic helix-loop-helix transcription factor NSCL-1 is dispensable for normal neuronal development. Krüger, M., Braun, T. Mol. Cell. Biol. (2002) [Pubmed]
  29. Expression of the helix-loop-helix genes Id-1 and NSCL-1 during cerebellar development. Duncan, M.K., Bordas, L., Dicicco-Bloom, E., Chada, K.K. Dev. Dyn. (1997) [Pubmed]
  30. Molecular cloning and characterization of a cDNA encoding a novel basic helix-loop-helix protein structurally related to Neuro-D/BHF1. Yasunami, M., Suzuki, K., Maruyama, H., Kawakami, H., Nagai, Y., Hagiwara, M., Ohkubo, H. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  31. The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts. Ihle, N.T., Paine-Murrieta, G., Berggren, M.I., Baker, A., Tate, W.R., Wipf, P., Abraham, R.T., Kirkpatrick, D.L., Powis, G. Mol. Cancer Ther. (2005) [Pubmed]
 
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