Dataset Information

Distinct transport and intracellular activities of two GlcAT-P isoforms.

ABSTRACT: A neural glycotope, human natural killer-1 carbohydrate, is involved in synaptic plasticity. The key biosynthetic enzyme is a glucuronyltransferase, GlcAT-P, a type II membrane protein comprising an N-terminal cytoplasmic tail, transmembrane domain, stem region, and C-terminal catalytic domain. Previously, we reported that GlcAT-P has two isoforms differing in only the presence or absence of the N-terminal 13 amino acids (P-N13) in the cytoplasmic tail, but the functional distinction of these two isoforms has not been reported. Herein, we show that when expressed in Neuro2A cells, short form GlcAT-P (sGlcAT-P) exhibited significantly higher glucuronylation activity than the longer form (lGlcAT-P), despite their comparable specific activities in vitro. In addition, sGlcAT-P was strictly localized in Golgi apparatus, whereas lGlcAT-P was mainly localized in Golgi but partly in the endoplasmic reticulum. We demonstrated that the small GTPase, Sar1, recognized a dibasic motif in the cytoplasmic tail near P-N13 that was important for exiting the endoplasmic reticulum, and Sar1 interacted with sGlcAT-P more strongly than lGlcAT-P. Finally, the attachment of P-N13 to another glycosyltransferase, polysialyltransferase-I (ST8Sia-IV), had similar effects, such as reduced activity and entrapment within endoplasmic reticulum. These results suggest that P-N13 can control glycosyltransferase transport through Sar1 binding interference.

SUBMITTER: Kizuka Y

PROVIDER: S-EPMC2666577 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Distinct transport and intracellular activities of two GlcAT-P isoforms.

Kizuka Yasuhiko Y Tonoyama Yasuhiro Y Oka Shogo S

The Journal of biological chemistry 20090130 14

A neural glycotope, human natural killer-1 carbohydrate, is involved in synaptic plasticity. The key biosynthetic enzyme is a glucuronyltransferase, GlcAT-P, a type II membrane protein comprising an N-terminal cytoplasmic tail, transmembrane domain, stem region, and C-terminal catalytic domain. Previously, we reported that GlcAT-P has two isoforms differing in only the presence or absence of the N-terminal 13 amino acids (P-N13) in the cytoplasmic tail, but the functional distinction of these tw ...[more]

PMID: 19181664

Similar Datasets

Project description:AP-2? is a transcription factor implicated in the regulation of differentiation and proliferation in certain tissues, including the mammary gland. In breast tumours, continued expression of AP-2? has been correlated with a better prognosis, but this is hard to reconcile with a reported role in the upregulation of the ERBB2 oncogene. The existence of TFAP2A isoforms, deriving from alternative first exons and differing in their N-terminal sequence, has been described in some mammals, but their relative abundance and activity has not been investigated in the human breast.Expression levels of four TFAP2A isoforms were assayed at the level of RNA and protein (via the generation of isoform-specific antibodies) in a panel of breast tumour cell lines and in tissue from normal breast and primary tumour samples. Expression constructs for each isoform were used in reporter assays with synthetic and natural promoters (cyclin D3 and ERBB2) to compare the activation and repression activity of the isoforms.We demonstrate that the two isoforms AP-2? 1b and AP-2? 1c, in addition to the originally cloned, AP-2? 1a, are conserved throughout evolution in vertebrates. Moreover, we show that isoform 1c in particular is expressed at levels at least on a par with the 1a isoform in breast epithelial lines and tissues and may be more highly expressed in tamoxifen resistant tumours. The isoforms share a similar transactivation mechanism involving the recruitment of the adaptors CITED2 or 4 and the transactivators p300 or CBP. However, isoform 1b and 1c are stronger transactivators of the ERBB2 promoter than isoform 1a. In contrast, AP-2? 1a is the only isoform able to act as a repressor, an activity that requires an intact sumoylation motif present within the N-terminus of the protein, and which the other two isoforms lack.Our findings suggest that TFAP2A isoforms may be differentially regulated during breast tumourigenesis and this, coupled with differences in their transcriptional activity, may impact on tumour responses to tamoxifen therapy. These data also have implications for the interpretation of tumour studies that seek to correlate outcomes with TFAP2A expression level.

Dataset Information

Distinct transport and intracellular activities of two GlcAT-P isoforms.

Publications

Distinct transport and intracellular activities of two GlcAT-P isoforms.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets