Hox proteins meet more partners

Current Opinion in Genetics and Development

Volumn 8, Issue 4, 1998, Pages 423-429

  Mann, Richard S ^a   Affolter, Markus ^b  

^a The New York Presbyterian Hospital   (United States)

^b UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

HOMEODOMAIN PROTEIN;

CELL FUNCTION; COMPLEX FORMATION; DEVELOPMENTAL BIOLOGY; DNA BINDING; DROSOPHILA; NONHUMAN; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALIA;

EID: 0031718145     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(98)80113-5     Document Type: Article

References (55)

1. McGinnis W, Krumlauf R: Homeobox genes and axial patterning. Cell 1992, 68:283-302.
2. Mann RS: The specificity of homeotic gene function. Bioessays 1995, 17:855-863.
3. Maconochie M, Nonchev S, Morrison A, Krumlauf R: Paralogous Hox genes: function and regulation. Annu Rev Genet 1996, 30:529-556.
4. Gehring W: Bildung eines vollstaendigen Mittelbeines mit Sternopleura in der Antennenregion bei der Mutante Nasobemia (Ns) von Drosophila melanogaster. Arch Klaus-Stift Vererb Forsch 1966, 41:44-54. [Title translation: Formation of a complete middle-leg with Sternopleura in the antennal region of the Drosophila melanogaster mutant Nasobemia (NS).]
5. Struhl G: A homoeotic mutation transforming leg to antenna in Drosophila. Nature 1981, 292:635-638.
6. Schneuwly S, Klemenz R, Gehring WJ: Redesigning the body plan of Drosophila by ectopic expression of the homoeotic gene Antennapedia. Nature 1987, 325:816-818.
7. Garcia-Bellido A: Homeotic and atavic mutations in insects. Amer Zool 1977, 17:613-630.
8. Lewis EB: A gene complex controlling segmentation in Drosophila. Nature 1978, 276:565-570.
9. Akam M: Hox genes and the evolution of diverse body plans. Phil Trans Soc Lond B 1995, 349:313-319.
10. Laughon A: DNA binding specificity of homeodomains. Biochemistry 1991, 30:11357-11367.
11. Gehring WJ, Affolter M, Burglin T: Homeodomain proteins. Annu Rev Biochem 1994, 63:487-526.
12. Sharkey M, Graba Y, Scott MP: Hox genes in evolution: protein surfaces and paralog groups. Trends Genet 1997, 13:145-151. Vertebrates have 13 Hox gene subgroups, called paralogs, and flies have 8 of these 13. Using the available Hox sequences, this paper derives consensus sequences for each of the 13 Hox paralogs, allowing distinguishing amino acids for each paralog to be defined. Those amino acids that are in the homeodomain were mapped onto the three-dimensional structure of the Antennapedia homeodomain. Strikingly, most of the paralog-specific differences are in surface residues, implying that they make contacts with other proteins.
13. Mann RS, Chan S-K: Extra specificity from extradenticle: the partnership between HOX and exd/pbx homeodomain proteins. Trends Genet 1996, 12:258-262.
14. Chan S-K, Mann RS: A structural model for an extradenticle-HOX-DNA complex accounts for the choice of HOX protein in the heterodimer. Proc Natl Acad Sci USA 1996, 93:5223-5228.
15. Chang C-P, Brocchieri L, Shen W-F, Largman C, Cleary M: Pbx modulation of Hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the HOX locus. Mol Cell Biol 1996, 16:1734-1745.
16. Shen WF, Chang CP, Rozenfeld S, Sauvageau G, Humphries RK, Lu M, Lawrence HJ, Cleary ML, Largman C: Hox homeodomain proteins exhibit selective complex stabilities with Pbx and DNA. Nucleic Acids Res 1996, 24:898-906.
17. Di Rocco G, Mavilio F, Zappavigna V: Functional dissection of a transcriptionally active, target-specific Hox-Pbx complex. EMBO J 1997, 16:3644-3654.
18. Knoepfler PS, Kamps MP: The highest affinity DNA element bound by Pbx complexes in t(1;19) leukemic cells fails to mediate cooperative DNA-binding or cooperative transactivation by E2a-Pbx1 and class 1 Hox proteins - evidence for selective targeting of E2a-Pbx1 to a subset of Pbx-recognition elements. Oncogene 1997, 14:2521-2531.
19. Lu Q, Kamps MP: Heterodimerization of Hox proteins with Pbx1 and oncoprotein E2a-Pbx1 generates unique DNA-binding specifities at nucleotides predicted to contact the N-terminal arm of the Hox homeodomain-demonstration of Hox-dependent targeting of E2a-Pbx1 in vivo. Oncogene 1997, 14:75-83.
20. Phelan ML, Featherstone MS: Distinct HOX N-terminal arm residues are responsible for specificity of DNA recognition by HOX monomers and HOX.PBX heterodimers. J Biol Chem 1997, 272:8635-8643.
21. Shanmugam K, Featherstone MS, Saragovi HU: Residues flanking the HOX YPWM motif contribute to cooperative interactions with PBX. J Biol Chem 1997, 272:19081-19087.
22. Shen W-F, Rozenfeld S, Lawrence H, Largman C: The Abd-B-like Hox homeodomain proteins can be subdivided by the ability to form complexes with Pbxla on a novel DNA target J Biol Chem 1997, 272:8198-8206.
23. Popperl H, Bienz M, Studer M, Chan SK, Aparicio S, Brenner S, Mann RS, Krumlauf R: Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell 1995, 81:1031-1042.
24. Chan S-K, Pöpperl H, Krumlauf R, Mann RS: An extradenticle-induced conformational change in a HOX protein overcomes an inhibitory function of the conserved hexapeptide motif. EMBO J 1996, 15:2477-2488.
25. Grieder N, Marty T, Ryoo H-D, Mann RS, Affolter M: Synergistic activation of a Drosophila enhancer by HOM/EXD and DPP signaling. EMBO J 1997, 16:7402-7410. In Drosophila, expression of the Hox gene labial in the endoderm is triggered by the signaling molecule Dpp, and lab550 is the enhancer in labial that responds to this molecule [50,51]. In this paper, lab550 is shown to contain a Labial-Exd binding site that is identical in 9 out of 10 positions to the Hoxb1-Pbx binding site in R3 from the Hoxb1 gene. Mutations in either the Labial or Exd half sites in this binding site destroy enhancer activity in vivo and prevent Dpp-mediated activation. It is suggested that lab550 integrates inputs from both Labial-Exd and from Dpp and that these two inputs synergize to activate transcription.
26. Chan S-K, Gould A, Krumlauf R, Mann R: Switching the in vivo specificity of a minimal Hox-responsive element. Development 1997, 124:2007-2014. Three copies of the 20 bp oligo, repeat 3 (R3), which was derived from the Hoxb1 autoregulatory enhancer (b1-ARE), can direct reporter gene expression in a labial-like pattern [24]. In this paper, a variant of R3, R3[TA], is shown to direct expression in a Deformed (Dfd)-like pattern. The only difference between R3 and R3[TA] is in the central two basepairs of the Exd-Hox binding site (from TGATGGATGG to TGATTAATGG). Expression of R3[TA] is dependent on Dfd and exd, consistent with it acting as an exd-dependent Dfd autoregulatory element. R3[TA]-like sequences present in Dfd autoregulatory elements can also dictate Dfd-like patterns when multimerized. These results suggest that small differences between Hox-PBC binding sites may be important for directing Hox-specific patterns of expression in vivo.
27. Neuteboom ST, Murre C: Pbx raises the DNA binding specificity but not the selectivity of antennapedia Hox proteins. Mol Cell Biol 1997, 17:4696-4706.
28. Biggin M, McGinnis W: Regulation of segmentation and segmental identity by Drosophila homeoproteins: the role of DNA binding in functional activity and specificity. Development 1997, 124:4425-4433.
29. Pinsonneault J, Florence B, Vaessin H, McGinnis W: A model for extradenticle function as a switch that changes HOX proteins from repressers to activators. EMBO J 1997, 16:2032-2042.
30. Moskow J, Bullrich F, Juebner K, Daar I, Buchberg A: Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice. Mol Cell Biol 1995, 15:5434-5443.
31. Nakamura T, Jenkins NA, Copeland NG: Identification of a new family of Pbx-related homeobox genes. Oncogene 1996, 13:2235-2242.
32. Rieckhof G, Casares F, Ryoo HD, Abu-Shaar M, Mann RS: Nuclear translocation of Extradenticle requires homothorax, which encodes an Extradenticle-related homeodomain protein. Cell 1997, 91:171-183. In this paper hth is shown to be important for Hox function in Drosophila and that hth is necessary and sufficient for the nuclear localization of Exd. hth encodes a TALE class homeodomain protein that is related to Exd and is highly homologous to murine Meis1 (also shown in [34,35]). GST pull-down experiments demonstrate that Hth and Meis1 can directly bind to Exd in vitro. These results suggest that the nuclear localization of Exd may be mediated by a direct interaction between Hth and Exd.
33. Steelman S, Moskow JJ, Muzynski K, North C, Druck T, Montgomery JC, Huebner K, Daar IO, Buchberg AM: Identification of a conserved family of Meis1-related homeobox genes. Gen Res 1997, 7:142-156.
34. Kurant E, Pai C-Y, Sharf R, Halachmi N, Sun Y, Salzberg A: dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS. Development 1998, 125:1037-1048.
35. Pai C-Y, Kuo T, Jaw T, Kurant E, Chen C, Bessarab D, Salzberg A, Sun Y: The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila. Genes Dev 1998, 12:435-446.
36. Berthelsen J, Zappavigna V, Mavilio F, Blasi F: Prep1, a novel functional partner of Pbx proteins. EMBO J 1998, 17:1423-1433. The Prep1 gene is cloned and shown to encode a TALE class homeodomain protein that is highly related to Meis1 and more weakly related to Exd. Prep1-Pbx1 dimers were shown to be the components of the transcription factor UEF2, which binds the sequence TGACAG in the uPA promoter. Domains that are required for the Prep-Pbx interaction are defined. Using the b1-ARE in a reporter construct, cotransfection experiments are used to show that Prep1 can stimulate Hoxb1-Pbx1-mediated transcriptional activation. Band-shift experiments are used to show that Prep1-Pbx-Hoxb1 complexes can assemble onto R3.
37. Bürglin T: A comprehensive classification of homeobox genes. In Guidebook to the Homeobox Genes. Edited by Duboule D. Oxford, UK: Oxford University Press; 1994:26-71.
38. Bürglin T: Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals. Nucleic Acids Res 1997, 25:4173-4180.
39. Chang CP, Jacobs Y, Nakamura T, Jenkins NA, Copeland NG, Cleary ML: Meis proteins are major in vivo DNA binding partners for wild-type but not chimeric Pbx proteins. Mol Cell Biol 1997, 17:5679-5687. Like Hth and Exd, Meis1 and Pbx can directly bind to each other in vitro and appear to be stable partners in cells. DNA-binding sites were selected for Meis1 alone and Meis1 + Pbx1 dimers. Interestingly, Pbx1-containing complexes isolated from cells select the binding site TGATTGAC (also shown in [18]), which is the same sequence that was selected by Meis1 + Pbx1. These results suggest that a large fraction of the Pbx1 in cells is complexed with a Meis-like protein. The region of Pbx required for the interaction with Meis1 is mapped to PBC-A domain, amino-terminal to the E2a fusion site in Pbx (Figure 1).
40. •], this paper shows that Meis1-Pbx1 dimers form on the site TGATTGAC and that this interaction requires the PBC-A domain. Similar interactions were shown to occur between pKnox1/Prep1 and Pbx1. In addition, this paper presents evidence that a hydrophobic heptad repeat in the HM domain of Meis1 is necessary for the interaction with Pbx1 (Figure 1).
41. Mann R, Abu-Shaar M: Nuclear import of the homeodomain protein Extradenticle in response to Decapentaplegic and Wingless signalling. Nature 1996, 383:630-633.
42. Azpiazu N, Morata G: Functional and regulatory interactions between Hox and extradenticle genes. Genes Dev 1998, 12:261-273.
43. Shen W-F, Montgomery J, Rozenfeld S, Moskow J, Lawrence H, Buchberg A, Largman C: AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins. Mol Cell Biol 1997, 17:6448-6458.
44. Chang CP, de Vivo I, Cleary ML: The Hox cooperativity motif of the chimeric oncoprotein E2a-Pbx1 is necessary and sufficient for oncogenesis. Mol Cell Biol 1997, 17:81-88.
45. •].
46. Casares F, Mann RS: Control of antennal versus leg development in Drosophila. Nature 1998, 392:723-726.
47. Weatherbee S, Halder G, Kim J, Hudson A, Carroll S: Ultrabithorax regulates genes at several levels of the wing-patterning hierarchy to shape the development of the Drosophila haltere. Genes Dev 1998, 12:1474-1482. This paper provides clear molecular examples of Hox-regulated differences between two homologous structures in the fly: the haltere and the wing. In the haltere, the Hox gene Ubx was shown to repress the expression of the signaling molecule Wg, as well as genes that are downstream of Wg. The findings suggest that Hox genes create morphological differences by regulating genes that are at many levels in the regulatory hierarchy, including secreted signaling molecules and downstream transcription factors.
48. Clandinin TR, Katz WS, Sternberg PW: Caenorhabditis elegans HOM-C genes regulate the response of vulval precursor cells to inductive signal. Dev Biol 1997, 182:150-161.
49. Maloof J, Kenyon C. The Hox gene lin-39 is required during C. elegans vulval induction to select the outcome of Ras signaling. Development 1998, 125:181-190. In C. elegans, signals from the anchor cell trigger the Ras signaling pathway in vulval precursor cells, signaling critical for vulval development. In this paper, the Hox gene lin-39 is also is shown to be required for vulval development, lin-39 appears to function by providing specificity to the Ras signaling pathway because when lin-39 is replaced by another Hox gene, mab-5, posterior structures are formed in place of the vulva. These results suggest that the Ras pathway, by itself, does not provide the information for making a vulva. Instead, Ras signaling appears to be interpreted differently by these two Hox genes.
50. Tremml G, Bienz M: Induction of labial expression in the Drosophila endoderm: response elements for dpp signalling and for autoregulation. Development 1992, 116:447-456.
51. Eresh S, Riese J, Jackson D, Bohmann D, Bienz M: A CREB-binding site as a target for decapentaplegic signaling during Drosophila endoderm induction. EMBO J 1997, 16:2014-2022.
52. Vachon G, Cohen B, Pfeifle C, McGuffin ME, Botas J, Cohen S: Homeotic genes of the Bithorax complex repress limb development in the abdomen of the Drosophila embryo through the target gene Distal-less. Cell 1992, 71:437-450.
53. Bürglin T: The PBC domain contains a MEINOX domain: coevolution of Hox and TALE homeobox genes? Dev Gene Evol 1998, 208:113-116.
54. Schuler GD, Altschul SF, Lipman DJ: A workbench for multiple alignment construction and analysis. Proteins: Structure, Function, and Genetics 1991, 9:180-190.
55. Chen H, Rossier C, Nakamura Y, Lynn A, Chakravarti A, Antonarakis SE: Cloning of a novel homeobox-containing gene, PKNOX1, and mapping to human chromosome 21q22.3. Genomics 1997, 41:193-200.