Sequence of MyD116 cDNA: a novel myeloid differentiation primary response gene induced by IL6

Abstract

EMBL accession no. X51829 cDNA clones of myeloid differentiation primary response (MyD) genes activated in the absence of protein sysnthesis in M1 myeloblastic leukemia cells induced for terminal differentiation by IL6, have been isolated (1). Here we report the full length nucleotide and deduced amino-acid sequences of MyDi 16, a novel MyD gene, which exhibits biphasic kinetics of expression, with an early peak (1 hr) and a decline followed by increased levels of steady state mRNA in terminally differentiated Ml cells (1). MyD 116 expression was observed also in murine bonemarrow, but not in non-myeloid tissues (1). MyD1 16 encodes for a 2.5 kb mRNA, having a very short 3' untranslated region with multiple AT3 motifs (underlined), implicated in mRNA destabilization (2). The MyDi 16 encoded protein (657aa) harbors 419 almost perfect 38aa long repeats (underlined), each containing a PEST region, characteristic of short lived proteins (3). The MyDi 16 protein does not contain protein secretory signals, transmembrane domains or known protein-DNA binding motifs; it contains, however, potential protein kinase phosphorylation sites (position 4, 181), amidation site (position 653), and 19 casein kinase II phosphorylation sites, including 3 in each repeat.

MyD genes in negative growth control

“…MyD88 mRNA was observed to rapidly accumulate following IL-6 stimulation (Lord et al, 1990c). High levels of MyD88 expression were observed in bone-marrow cells, suggesting a role for this gene in blood cell development.…”

“…MyD116 is the second novel MyD gene that was isolated in our laboratory (Lord et al, 1990b). Like other MyD genes it is rapidly induced by IL-6 in M1, and expressed in bone-marrow cells.…”

MyD88: A Critical Adaptor Protein in Innate Immunity Signal Transduction

“…Both papers relate to the identification of MyD88 as an essential adaptor protein in the IL-1R1 signaling pathway (5,6). MyD88 was first identified as a myeloid differentiation primary response gene in 1990 (7). Subsequently, Dan Hultmark was the first to notice amino acid homology between MyD88 and the cytoplasmic domains of Drosophila Toll and mammalian IL-1 receptors, leading him to suggest that "MyD88 may define a family of signal transduction molecules with an ancestral function in the activation of the immune system" (8).…”

The γ 1 34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase

“…The carboxyl-terminal amino acids of ␥ 1 34.5 are homologous to the corresponding domains of highly conserved mammalian protein known as GADD34 (growth arrest and DNA damage protein 34) (7)(8)(9)(10)(11). The murine GADD34 gene known as MyD116 contains 657 aa and consists of a large basic aminoterminal domain, a 38-aa sequence repeated 4.5 times, and a carboxyl terminus that can substitute for the corresponding domain of the ␥ 1 34.5 to prevent the shutoff of protein synthesis (9)(10)(11)(12).…”

“…The murine GADD34 gene known as MyD116 contains 657 aa and consists of a large basic aminoterminal domain, a 38-aa sequence repeated 4.5 times, and a carboxyl terminus that can substitute for the corresponding domain of the ␥ 1 34.5 to prevent the shutoff of protein synthesis (9)(10)(11)(12).…”