No abstract

Onzin is a small, novel, and highly conserved protein with unique structure and tissue-restricted expression. The regulation of its expression and biological roles remain greatly elusive. Here, we provide the first demonstration that onzin expression is significantly downregulated during differentiation induction of acute myeloid leukemic (AML) cell lines and primary cells by all-trans retinoic acid (ATRA) and especially by phorbol 12-myristate 13-acetate (PMA). Applying chemical inhibitions, RNA interferences, and transfected expressions of dominant negative mutants or constitutive catalytic forms of the related kinases, we show that protein kinase C-e (PKCe)-extracellular signal-regulated protein kinase 2 (ERK2) signaling axis is required for PMA-induced downregulation of onzin expression. The ectopic expression of onzin partially inhibits PMA-induced monocytic differentiation of AML cells, whereas suppression of onzin by specific short hairpin RNAs enhances PMA-induced differentiation to a degree. Furthermore, onzin partially inhibits the transcriptional activity of hematopoiesisrelated important transcription factor PU.1 via their interaction. Taken together, our results show that PMA downregulates onzin expression through PKCe-ERK2 signaling pathway, which favors monocytic differentiation of leukemic cells.

No abstract

Psoriasis is a chronic disease characterized by keratinocyte hyperproliferation and inflammation. It has been demonstrated that the expression of calcitonin gene-related peptide (CGRP) is elevated in psoriasis lesions and CGRP-containing neuropeptide nerve fibers are denser in the psoriatic epidermis. CGRP has been previously described to influence proliferation of several cell types, such as Schwann cell, tracheal epithelial cells, and human gingival fibroblasts. In the present study, we determined the effect of CGRP on HaCaT keratinocyte proliferation and the role of mitogen-activated protein kinases (MAPKs) in CGRP induced keratinocyte proliferation. Our data indicate CGRP increased [(3)H]-thymidine incorporation and MTT activity of HaCaT in a concentration-dependent manner. CGRP also enhanced serum-induced HaCaT cell proliferation. HaCaT cells cultured with CGRP had a significant increase in phosphorylated ERK1/2, p38 and JNK, and CGRP induced DNA synthesis was inhibited by PD 98059 or SB 203580, selective inhibitors of MAP kinase kinase (MEK, which is upstream from ERK) and p38, respectively. These findings suggest that HaCaT cell proliferate in response to CGRP, which is mediated by phosphorylation of ERK1/2 and p38 MAPK.

No abstract