Trans-acting Factors Regulate the Expression of CD44 Splice Variants

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1996 Aug 1

PMID 8670907

Citations 25

Authors

H Konig

J Moll

H Ponta

P Herrlich

Affiliations

Soon will be listed here.

Abstract

Variant isoforms of the cell surface glycoprotein CD44 (CD44v) are expressed during development, in selected adult tissues and in certain metastatic tumor cells. CD44v differ from the standard isoform (CD44s) by up to ten additional exon sequences included by alternative splicing. By cell fusion experiments, we have obtained evidence for the existence of cell-type specific trans-acting factors recruiting CD44 variant exon sequences. Stable cell hybrids of CD44s and CD44v expressing cells indicated a dominant mechanism for variant-exon inclusion. In transient interspecies heterokaryons of human keratinocytes and rat fibroblasts, the ability of the keratinocytes to include all variant exon sequences in CD44 was conferred completely on the rat fibroblast nucleus. Fusions of cells with complex CD44 splice patterns do not permit interpretation of splice control by the relative abundance of a single trans-acting factor, but rather by (a) positively acting factor(s) recruiting variant exon sequences in the 3' to 5' direction and additional factors selecting individual exons. Since the pancreatic carcinoma cell line BSp73ASML (in contrast to the cervix carcinoma cell lines SiHa and ME180) could not transfer its specific splice pattern in cell fusions, we conclude that in some tumors, splicing is also controlled by mutation of cis-acting recognition sites.

Citing Articles

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Differential recruitment of CD44 isoforms by ErbB ligands reveals an involvement of CD44 in breast cancer.

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Transforming growth factor β1 (TGFβ1) regulates CD44V6 expression and activity through extracellular signal-regulated kinase (ERK)-induced EGR1 in pulmonary fibrogenic fibroblasts.

Ghatak S, Markwald R, Hascall V, Dowling W, Lottes R, Baatz J J Biol Chem. 2017; 292(25):10465-10489.

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CD44 mediates the catch-bond activated rolling of HEPG2Iso epithelial cancer cells on hyaluronan.

Hanke-Roos M, Fuchs K, Maleschlijski S, Sleeman J, Orian-Rousseau V, Rosenhahn A Cell Adh Migr. 2016; 11(5-6):476-487.

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Zhang P, Feng S, Liu G, Wang H, Fu A, Zhu H Oncogene. 2016; 35(38):5056-5069.

PMID: 27041584 PMC: 5033661. DOI: 10.1038/onc.2016.67.

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