NDLI: Alternative mRNA Splicing Generates Two Distinct ADAM12 Prodomain Variants

Content Provider	PubMed Central
Author	Sara, Duhachek-muggy Hui, Li Yue, Qi Anna, Zolkiewska
Editor	Buratti, Emanuele
Copyright Year	2013
Abstract	Human ADAM12, transcript variant 1 (later on referred to as Var-1b), present in publicly available databases contains the sequence 5′-GTAATTCTG-3′ at the nucleotide positions 340–348 of the coding region, at the 3′ end of exon 4. The translation product of this variant, ADAM12-Lb, includes the three amino acid motif 114VIL116 in the prodomain. This motif is not conserved in ADAM12 from different species and is not present in other human ADAMs. Currently, it is not clear whether a shorter variant, Var-1a, encoding the protein version without the 114VIL116 motif, ADAM12-La, is expressed in human. In this work, we have established that human mammary epithelial cells and breast cancer cells express both Var-1a and Var-1b transcripts. Importantly, the proteolytic processing and intracellular trafficking of the corresponding ADAM12-La and ADAM12-Lb proteins are different. While ADAM12-La is cleaved and trafficked to the cell surface in a manner similar to ADAM12 in other species, ADAM12-Lb is retained in the ER and is not proteolytically processed. Furthermore, the relative abundance of ADAM12-La and ADAM12-Lb proteins detected in several breast cancer cell lines varies significantly. We conclude that the canonical form of transmembrane ADAM12 is represented by Var-1a/ADAM12-La, rather than Var-1b/ADAM12-Lb currently featured in major sequence databases.
Related Links	http://dx.doi.org/10.1371/journal.pone.0075730
Starting Page	75730
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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