Identification of a novel gene expressed in activated natural killer cells and T cells.

Abstract

We have isolated a cDNA clone from a human activated NK cell-derived cDNA library that identifies a transcript (NK4) that is selectively expressed in lymphocytes. The expression of this transcript is increased after activation of T cells by mitogens or activation of NK cells by IL-2 (lymphokine-activated killer cells). The transcript levels demonstrated by Northern blot analysis increase by 12 h after activation, remain high for at least 48 h, and require protein synthesis for expression. Southern blot analysis of B lymphoblastoid lines derived from 18 unrelated individuals reveal variable banding patterns suggestive of polymorphism within the NK4 gene. No homology was found between the sequence of the coding region of this transcript and any sequences in the GenBank data base. Sequence homology to the U1 small nuclear RNA was found within the 3' untranslated region immediately upstream of the site of polyadenylation, suggesting a possible role for U1 in the polyadenylation process. Sequence analysis indicates the transcript would encode a protein having a mass of 27 kDa. The presence of a signal sequence and lack of a transmembrane region suggests that the protein is secreted. In addition, the protein contains an RGD sequence that may be involved in cellular adhesion. This transcript appears to encode a novel product common to the activation pathways of both NK cells and T cells.

The pro-tumorigenic cytokine IL-32 has a high turnover in multiple myeloma cells due to proteolysis regulated by oxygen-sensing cysteine dioxygenase and deubiquitinating enzymes

“…We found that regulation of IL-32 by ubiquitination-dependent proteasomal degradation and reversing the process by deubiquitinating enzymes are also found in healthy cells of the lymphocyte lineage, as demonstrated with primary T cells. IL-32 is highly expressed by activated T cells ( 35 – 38 ). DUBs are currently exploited as therapeutic targets in different cancers ( 23 , 39 – 41 ), but they may also influence the cancer microenvironment, including T cells ( 42 ).…”

Natural killer cells in sepsis: Friends or foes?

“…It modulates the activation of other immune cells, such as macrophages or dendritic cells, enabling them to perform comprehensive anti-bacterial responses ( 92 , 93 ). Moreover, IL-32, previously named as NK cell transcript 4 (NK4), can be produced by NK cells when activated by IL-2 ( 94 , 95 ). It also stimulates inflammatory responses by inducing monocytes or macrophages to secrete various cytokines, including TNF-α, IL-1β, IL-6 or IL-8 ( 96 ).…”

Pan-cancer analysis reveals IL32 is a potential prognostic and immunotherapeutic biomarker in cancer

“…The development of malignant tumors is related to a variety of factors, and monitoring tumor occurrence, early prevention, and timely control of tumors is important for human health 1 , 2 . Inflammation plays a crucial role in carcinogenesis and affects the development of malignant tumors and invasive metastasis.…”