AN ALTERNATIVE SPLICE VARIANT OF MKP-2 TRANSCRIPT IS EXPRESSED IN A NON-SMALL-CELL LUNG CANCER CELL LINE.

COHEN SABBAN JM; MORI SEQUEIROS GARCÍA MM; NUDLER S; PAZ C

Buenos Aires

Congreso; LXII Annual Meeting of Argentine Society of Clinical Investigation; 2017

SAIC, SAIB, SAI, SAFE, SAA, SAB, SAFIS, SAH, SAP

MAP kinases (MAPK) ERKs, JNKs and p38 are activated by dualphosphorylation and regulate several processes such as proliferation,differentiation and apoptosis. Given that MAPK phosphatase(MKP) family members inactivate MAPK, they are potential modulatorsof MAPK-dependent processes. MKP-2 (or DUSP4) is anuclear dual activity phosphatase able to dephosphorylate JNK1/2and ERK1/2 and induced by stress conditions. An alternative splicevariant of MKP-2 transcript and protein were found in PC3 prostateand MDA-MB-231 breast cancer cells and human prostate biopsies.This variant, generated by exon skipping and referred to asthe S or short variant, displays phosphatase activity but lacks severalmotives involved in the subcellular localization and regulation.Thus, the L (complete) and S variants could have different biologicalroles, even though the characterization of the S transcript has notbeen fully elucidated yet. We analyzed transcript expression in nonsmall-cell lung cancer cell line A549. RT-PCR analysis showed atime-dependent increase in L and S transcripts after cell stimulationwith 0.1 μg/mL LPS (bacterial lipopolysaccharides), a stimulus ableto induce MKP-2 L. The L transcript rendered a three-fold increasevs. control after 1 h (P