Isolation of interleukin 2-induced immediate-early genes.

Abstract

Clonal expansion of antigen-reactive T lymphocytes is driven by the lymphokine interleukin 2 (IL-2). To further elucidate the mechanisms of IL-2 action, we have utilized a differential hybridization procedure to clone IL-2-induced immediate-early genes from an IL-2-stimulated human T-cell cDNA library. To increase the frequency of IL-2-induced transcripts represented in the library, the protein synthesis inhibitor cycloheximide was included during the 2-hr IL-2 stimulation to superinduce gene expression, and the uridine analogue 4-thiouridine was utilized to enable selective purification of newly synthesized transcripts. From the enriched library, we have isolated eight IL-2-induced genes, six of which represent previously unrecognized human sequences. Northern blot analysis revealed that the induction of seven of the genes is specific to the IL-2-mediated G1 "progression" phase of the cell cycle, in that only one gene is also induced during the T-celi receptor-triggered Gr-G1 "competence" phase. These results indicate that the effects of IL-2 are mediated by the specific induction of a number of immediateearly genes and provide a means with which to further delineate the mechanisms whereby IL-2 stimulates T-lymphocyte proliferation and differentiation. The methods described in this report should also be of general utility in the dissection of the signaling pathways activated by diverse cytokine receptors.

Molecular Responses of Human Lung Epithelial Cells to the Toxicity of Copper Oxide Nanoparticles Inferred from Whole Genome Expression Analysis

“…GADD45B and GADD45G are members of the GADD45 family of proteins that are induced by genotoxic stresses and various apoptotic cytokines [11][12][13] and are involved in cell cycle arrest, [14][15][16][17][18][19] DNA repair, [20][21][22] cell survival, [22][23][24][25][26][27] and apoptosis. These functions are mediated by proliferating cell nuclear antigen (PCNA), cell division control 2 (CDC2), cyclin B1 (CCNB1), and cyclin-dependent kinase inhibitor 1A (CDKN1A; also known as p21), which are classified in the GO "cell cycle" category.…”

MyD genes in negative growth control

“…The proteins encoded by these genes are 57% identical, indicating that MyD118 and Gadd45 represent two separate but closely related genes . A third member in the MyD118 gene family, CR6, has been cloned as well (Beadling et al, 1993;and unpublished).…”

Hematopoietic cells from gadd45a-deficient and gadd45b-deficient mice exhibit impaired stress responses to acute stimulation with cytokines, myeloablation and inflammation

“…Overall, Gadd45a, Gadd45b and Gadd45g have been implicated in cell cycle arrest (Beadling et al, 1993;Hollander et al, 1999;Wang et al, 1999;Zhang et al, 1999), DNA repair (Smith et al, 1994;Vairapandi et al, 1996), apoptosis (Harkin et al, 1999;Vairapandi et al, 2000;Azam et al, 2001;Takekawa et al, 2002;Yoo et al, 2003), cell survival (Smith et al, 1996;De Smaele et al, 2001;Zazzeroni et al, 2003;Papa et al, 2004;Gupta et al, 2005), genomic stability (Hollander et al, 1999), inflammatory response and innate immunity (Lu et al, 2001;Yang et al, 2001;Lu et al 2004). Gadd45 proteins have been shown to stimulate the p38-c-Jun N-terminal kinase (JNK) mitogen-activated protein (MAP) kinase pathways in response to stress situations and thereby sensitize cells for growth arrest, apoptosis or survival (Takekawa and Saito, 1998;Harkin et al, 1999;De Smaele et al, 2001;Lu et al, 2001;Hildesheim et al, 2002;Yoo et al, 2003).…”