title: The BTB-kelch protein LZTR-1 is a novel Golgi protein that is degraded upon induction of apoptosis.
abstract: Members of the BTB-kelch superfamily play important roles during fundamental cellular processes, such as the regulation of cell morphology, migration, and gene expression. The BTB-kelch protein LZTR-1 is deleted in the majority of DiGeorge syndrome patients and is believed to act as a transcriptional regulator. However, functional and expression profiling studies of LZTR-1 have not been performed thus far. Therefore, we examined the subcellular localization and function of LZTR-1 to gain insights into its biological role. Analysis of the primary structure of the protein revealed six N-terminal kelch motifs and two BTB/POZ domains at the C terminus within LZTR-1. Confocal analysis of the subcellular distribution of LZTR-1 using the Golgi markers GM130, Golgin-97, and TGN46 identified a localization of LZTR-1 exclusively on the cytoplasmic surface of the Golgi network that is mediated by its second BTB/POZ domain. In contrast to most other BTB-kelch proteins, LZTR-1 did not co-localize with actin. Treatment with brefeldin A did not lead to redistribution of LZTR-1 to the endoplasmic reticulum but caused its relocalization in dispersed, punctuated structures that were also positive for GM130. These data demonstrate that LZTR-1 is a Golgi matrix-associated protein. Upon induction of apoptosis, LZTR-1 was phosphorylated on tyrosine residues and subsequently degraded; that could be rescued partially by the addition of the caspase inhibitor Z-VAD-fmk and the proteasome inhibitors lactacystin and MG132. Taken together, our experiments identify LZTR-1 as the first BTB-kelch protein that exclusively localizes to the Golgi network, and the binding of LZTR-1 to the Golgi complex is mediated by its second BTB/POZ domain.
authors.affiliation: Department of Vascular Biology and Angiogenesis Research, Tumor Biology Center Freiburg, 79106 Freiburg, Germany.
authors.forename: Tanju G
authors.initials: TG
authors.lastname: Nacak
authors.forename: Kerstin
authors.initials: K
authors.lastname: Leptien
authors.forename: Doris
authors.initials: D
authors.lastname: Fellner
authors.forename: Hellmut G
authors.initials: HG
authors.lastname: Augustin
authors.forename: Jens
authors.initials: J
authors.lastname: Kroll
mesh_terms: D000199:Actins / Q000737:chemistry; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis; D001324:Autoantigens / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D020126:Brefeldin A / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D006367:HeLa Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D000199:Actins; D000590:Amino Acid Chloromethyl Ketones; D001324:Autoantigens; D000077614:Golgi Matrix Proteins; C450721:Golgi complex autoantigen, 97-kDa; C097741:Golgin subfamily A member 2; C509917:LZTR1 protein, human; D007976:Leupeptins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C072237:TGOLN2 protein, human; D014157:Transcription Factors; D025801:Ubiquitin; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020126:Brefeldin A; D014443:Tyrosine; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde