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Target Concepts:
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Query: UNIPROT:P17931 (
galectin-3
)
2,860
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Galectin-3
, a beta-galactoside-binding protein, is implicated in cell growth, adhesion, differentiation, and tumor progression by interactions with its ligands. Recent studies have revealed that
galectin-3
suppresses apoptosis and anoikis that contribute to cell survival during metastatic cascades. Previously, it has been shown that human
galectin-3
undergoes post-translational signaling modification of Ser(6) phosphorylation that acts as an "on/off" switch for its sugar-binding capability. We questioned whether
galectin-3
phosphorylation is required for its anti-apoptotic function. Serine to alanine (S6A) and serine to glutamic acid (S6E) mutations were produced at the casein kinase I phosphorylation site in
galectin-3
. The cDNAs were transfected into a breast carcinoma cell line BT-549 that innately expresses no
galectin-3
. Metabolic labeling revealed that only wild type
galectin-3
undergoes phosphorylation in vivo. Expression of Ser(6) mutants of
galectin-3
failed to protect cells from cisplatin-induced cell death and poly(ADP-ribose) polymerase from degradation when compared with wild type
galectin-3
. The non-phosphorylated
galectin-3
mutants failed to protect cells from anoikis with G(1) arrest when cells were cultured in suspension. In response to a loss of cell-substrate interactions, only cells expressing wild type
galectin-3
down-regulated cyclin A expression and up-regulated
cyclin D
(1) and cyclin-dependent kinase inhibitors, i.e. p21(WAF1/CIP1) and p27(KIP1) expression levels. These results demonstrate that
galectin-3
phosphorylation regulates its anti-apoptotic signaling activity.
...
PMID:Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest. 1172 77
Galectin-3
is a multifunctional carbohydrate-binding protein found in the nucleus, cytoplasm and the extracellular milieu. Nuclear
galectin-3
expression is associated with cell proliferation, and its role in pre-mRNA splicing has been suggested. In this report, we investigated the role of
galectin-3
on
cyclin D
(1) gene expression, a critical inducer of the cell cycle and a potential oncogene in human cancer. We found that
galectin-3
induces
cyclin D
(1) promoter activity in human breast epithelial cells independent of cell adhesion through multiple cis-elements, including the SP1 and CRE sites. We present evidence that
galectin-3
induction of the
cyclin D
(1) promoter may result from enhancement/stabilization of nuclear protein-DNA complex formation at the CRE site of the
cyclin D
(1) promoter. We also show that
galectin-3
co-operates with, but does not depend on, pRb for
cyclin D
(1) promoter activation. The present study reveals a growth promoting activity of
galectin-3
through
cyclin D
(1) induction, and suggests a novel function of nuclear
galectin-3
in the regulation of gene transcription.
...
PMID:Galectin-3 enhances cyclin D(1) promoter activity through SP1 and a cAMP-responsive element in human breast epithelial cells. 1243 50
The relationship between
galectin-3
and p27
kip1
protein expression levels in cervical precancerous lesions and clinical prognosis were studied. A total of 74 patients with cervical intraepithelial neoplasia [(CIN), 20 cases classified as stage I, 24 cases as stage II and 30 cases as stage III] were enrolled in this study. Tissue
galectin-3
, p27
kip1
, vascular endothelial growth factor (VEGF)-2 and
cyclin D
protein levels were detected via immunohistochemical staining and reverse transcription polymerase chain reaction (PCR). Follow-up median duration was 13.5 months and recurrence rate was determined.
Galectin-3
, VEGF-2, and
cyclin D
expression was elevated in patients with higher stage CIN, whereas p27
kip1
showed the opposite trend (p<0.05). During follow-up, there were 3 cases (15.0%) of recurrence in the CIN-I group, 5 cases (20.8%) in the CIN-II group and 9 cases (30.0%) in CIN-III the group. No significant difference in recurrence rate was noted among the groups (p>0.05). The upregulation of
galectin-3
and downregulation of p27
kip1
in CIN tissues may be related to tumor progression. This phenomenon will require further verification.
...
PMID:The relationship between cervical precancerous lesion galectin-3 and p27 protein expression and clinical prognosis. 2943 47