Disease relevance of HOXC5

• HOX3D is developmentally regulated during embryogenesis and is activated by retinoic acid (RA) in cultured embryonal carcinoma (EC) cells [1].
• This might suggest a role for HOXC5 in the pathogenesis of these lymphomas [2].
• Thus, mainly mature lymphoid cell lines and neoplastic cells of NHL do express HOXC5, in contrast to the lack of expression in normal lymphoid cells and leukemias [3].
• Furthermore, the presence of HOXC5 and HOXC6 expression specifically in skin infiltrates of late differentiation stages of myeloid leukemias, suggests an additional role for these genes in the positioning of these myeloid cells in skin tissue [4].
• An indolicidin analogue CP-11, ILKKWPWWPWRRK-NH(2), with improved activity against Gram-negative bacteria had increased positive charge and amphipathicity while maintaining the short length of the parent molecule [5].

High impact information on HOXC5

• The HOX3D protein, and those encoded by the downstream gene HOX3E and its paralog HOX4B are instead inactive [1].
• The upstream region of the human homeobox gene HOX3D is a target for regulation by retinoic acid and HOX homeoproteins [1].
• Transfection of HOX3D upstream genomic sequences linked to a reporter gene allowed the functional definition of its promoter, containing a canonical TATA element [1].
• These results indicate that, in contrast to HOXC4 and HOXC6, HOXC5 shows a type- and site-restricted expression pattern in both T- and B-cell NHLs [6].
• In contrast, HOXC5 is not expressed in the lymphoid lineage, but was found in lymphoid cell lines, representing the neoplastic equivalents of various differentiation stages of T and B lymphocytes [6].

Biological context of HOXC5

• We studied the structure, regulation and expression of HOX3D, a human homeobox gene located in the HOX3 cluster on chromosome 12 [1].
• In contrast, HOXC5 gene expression was found in only 6/32 AMLs [4].
• RESULTS: C16476T polymorphism was not detected; A17860G located in 3' flanking sequence of HOXC5 gene displayed significant difference between the two groups [7].
• HOX3 contains at least 7 homeoboxes in 160 kb on chromosome 12 [8].
• The finished sequence from BAC clones from the genome of the sea urchin, Strongylocentrotus purpuratus, reveals a gene order wherein the anterior genes (Hox1, Hox2 and Hox3) lie nearest the posterior genes in the cluster such that the most 3' gene is Hox5 [9].

Anatomical context of HOXC5

• Interestingly, a strong expression of HOXC5 in primary anaplastic CD30+ large T-cell lymphomas was found [2].
• In contrast, HOXC5 was specifically expressed in a subset of B-cell non-Hodgkin's lymphomas (B-NHL) but not in normal lymphocytes or lymphoid leukemias [2].
• Furthermore, HOXC5 expression was consistently absent in reactive cutaneous lymphoid infiltrates, hyperplastic tonsils and lymph nodes, and peripheral blood lymphocytes either unstimulated or stimulated by a cocktail of CD3 and CD28 antibodies [2].
• However, HOXC5 is only expressed in neoplastic cell lines and in neoplastic cells of NHL, but not in CD34+ BM cells, nor in resting or activated lymphoid cells isolated from tonsil, PB, or in leukemia cells [3].
• Expression of HOXC4, HOXC5, and HOXC6 in human lymphoid cell lines, leukemias, and benign and malignant lymphoid tissue [3].

Associations of HOXC5 with chemical compounds

• A structural comparison of CP-11 and cycloCP-11 revealed that the higher trypsin resistance of cycloCP-11 may be due to the more compact packing of lysine and tryptophan side chains [5].
• The structure of CP-11 in the presence of dodecylphosphocholine (DPC) micelles was determined using nuclear magnetic resonance spectroscopy [5].

Other interactions of HOXC5

• In the present study the expression of HOXC4, HOXC5, and HOXC6 in primary cutaneous lymphomas was investigated [2].
• Recently, we have demonstrated that HOXC4 and HOXC6, but not HOXC5, are expressed during lymphoid differentiation [4].
• Our data add weight to the body of evidence attributing to a specific adult tissue a particular combination of expressed HOX genes and suggest that HOXC5 and/or HOXC8 could be involved in the process leading to the transformation of cervical keratinocytes [10].

Analytical, diagnostic and therapeutic context of HOXC5

• However, by semiquantitative RT-PCR these lymphomas showed a weak expression of HOXC5 mRNA [2].
• The HOXC5 and HOXC8 expression was also observed in two other transformed keratinocytes cell lines of independent origins, Eil-8 and 18-11S3, and confirmed by in situ hybridization [10].
• Both CP-11 and cycloCP-11 associated with phospholipid membranes in a similar manner as indicated by circular dichroism and fluorescence spectra [5].

References