Karyopherins in nuclear transport of homeodomain proteins during development

Ye, Wenduo; Lin, Weiyi; Tartakoff, Alan M.; Tao, Tao

doi:10.1016/j.bbamcr.2011.01.013

Cited by 18 publications

(15 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, in our IHC analysis, we detected PITX2 signaling in the cytoplasm in both ESCC and adjacent non‐neoplastic tissues, although at different levels. By reviewing the literature, we found that altered intracellular localization of PITX2 is not uncommon, either because of destabilization of the homeodomain or a result of loss of potential nuclear localization signal 44, 45. For example, in Murine C2C12 myoblasts, PITX2 displays a predominant cytoplasmic localization and is necessary to ensure proper cellular proliferation and differentiation 46.…”

Section: Discussionmentioning

confidence: 99%

PITX2: A promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma

Zhang

Tong

Yang

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

The paired-like homeodomain transcription factor 2 (PITX2), a downstream effector of wnt/b-catenin signaling, is well known to play critical role during normal embryonic development. However, the possible involvement of PITX2 in human tumorigenesis remains unclear. In this study, we extend its function in human esophageal squamous cell carcinoma (ESCC). The real-time PCR, Western blotting and immunohistochemistry (IHC) methods were applied to examine expression pattern of PITX2 in two different cohorts of ESCC cases treated with definitive chemoradiotherapy (CRT). Receiver operating characteristic (ROC) curve analysis was used to determine the cutoff point for PITX2 high expression in the training cohort. The ROC-derived cutoff point was then subjected to analyze the association of PITX2 expression with patients' survival and clinical characteristics in training and validation cohort, respectively. The expression level of PITX2 was significantly higher in ESCCs than that in normal esophageal mucosa. There was a positive correlation between PITX2 expression and clinical aggressiveness of ESCC. Importantly, high expression of PITX2 was observed more frequently in CRT resistant group than that in CRT effective group (p < 0.05). Furthermore, high expression of PITX2 was associated with poor disease-specific survival (p < 0.05) in ESCC. Then, the MTS, clonogenic survival fraction and cell apoptosis experiments showed that knockdown of PITX2 substantially increased ESCC cells sensitivity to ionizing radiation (IR) or cisplatin in vitro. Thus, the expression of PITX2, as detected by IHC, may be a useful tool for predicting CRT resistance and serves as an independent molecular marker for poor prognosis of ESCC patients treated with definite CRT.Esophageal squamous cell carcinoma (ESCC) is one of the most common incident cancers, which accounts for a significant number of cancer-related deaths in worldwide. 1,2 Recently, for those thoracic cases with locally advanced disease, definitive chemoradiotherapy (CRT) is an important component of the therapeutic strategy. 3,4 Even if the great achievement has accomplished in diagnostic development and radiotherapy advance, the overall 5-year survival rate of ESCC patients is still unsatisfactory. [5][6][7] The high rate of recurrence and metastasis is closely related with the inferior quality of survival outcome. Currently, only the stage based on tumor node metastases classification and primary complete response (CR) to CRT are widely accepted as prognostic factors. However, the clinical responses of ESCC to CRT are various, and the survival rate between patients with the same clinical stage and/or CRT response is quite different. 8,9 Therefore, there is still an urgent need to identify novel promising markers that could precisely predict tumor response to CRT and further stratify ESCC patient survival outcome.The paired-like homeodomain transcription factor 2 (PITX2) gene, located in chromosome 4q25-a27, encodes a transcription factor of the paired-like homeodomain protein fam...

show abstract

Section: Discussionmentioning

confidence: 99%

PITX2: A promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma

Zhang

Tong

Yang

et al. 2012

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…To assess the practical utility of Q‐SCAn to examine a classical signaling paradigm for multicompartment protein localization, the movement of a transcription factor from the cytoplasm to the nucleus , we analyzed the localization of the S. cerevisiae transcription factor, Yap1 . Under normal cellular conditions, Yap1 shuttles between the nucleus and the cytoplasm but shows diffuse, steady‐state localization primarily to the cytoplasm, as the rate of nuclear export exceeds the rate of nuclear import .…”

Section: Resultsmentioning

confidence: 99%

Automated Quantification of the Subcellular Localization of Multicompartment Proteins via Q‐SCAn

Bauer

Corbett

Doetsch

2013

Traffic

View full text Add to dashboard Cite

In eukaryotic cells, proteins can occupy multiple intracellular compartments and even move between compartments to fulfill critical biological functions or respond to cellular signals. Examples include transcription factors that reside in the cytoplasm but are mobilized to the nucleus as well as dual-purpose DNA repair proteins that are charged with simultaneously maintaining the integrity of both the nuclear and mitochondrial genomes. While numerous methods exist to study protein localization and dynamics, automated methods to quantify the relative amounts of proteins that occupy multiple subcellular compartments have not been extensively developed. To address this need, we present a rapid, automated method termed Quantitative Subcellular Compartmentalization Analysis (Q-SCAn). To develop this method, we exploited the facile molecular biology of the budding yeast, Saccharomyces cerevisiae. Individual subcellular compartments are defined by a fluorescent marker protein and the intensity of a target GFP-tagged protein is then quantified within each compartment. To validate Q-SCAn, we analyzed relocalization of the transcription factor Yap1 following oxidative stress and then extended the approach to multi-compartment localization by examining two DNA repair proteins critical for the base excision repair pathway, Ntg1 and Ung1. Our findings demonstrate the utility of Q-SCAn for quantitative analysis of the subcellular distribution of multi-compartment proteins.

show abstract

“…Intriguingly, their HD signature structure is important for both their DNA binding ability and their nucleocytoplasmic trafficking [14]. The accurate nucleocytoplasmic distribution of these proteins is essential for their functioning [15].…”

Section: Discussionmentioning

confidence: 99%

Nuclear localization of Obox4 is dependent on its homeobox domain

Park

Lee

2013

Clin Exp Reprod Med

View full text Add to dashboard Cite

ObjectiveOocyte-specific homeobox 4 (Obox4) is preferentially expressed in oocytes and plays an important role in the completion of meiosis of oocytes. However, the Obox4 expression pattern has not been reported yet. In this study, we investigated the subcellular localization of Obox4 using a green fluorescent protein (GFP) fusion expression system.MethodsThree regions of Obox4 were divided and fused to the GFP expression vector. The partly deleted homeodomain (HD) regions of Obox4 were also fused to the GFP expression vector. The recombinant vectors were transfected into HEK-293T cells plated onto coated glass coverslips. The transfected cells were stained with 4',6-diamidino-2-phenylindol and photographed using a fluorescence microscope.ResultsMutants containing the HD region as well as full-length Obox4 were clearly localized to the nucleus. In contrast, the other mutants of either the N-terminal or C-terminal region without HD had impaired nuclear localization. We also found that the N-terminal and C-terminal of the Obox HD contributed to nuclear localization and the entire HD was necessary for nuclear localization of Obox4.ConclusionBased on the results of the present study, we demonstrated that the intact HD region of Obox4 is responsible for the nuclear localization of Obox4 protein in cells.

show abstract

Karyopherins in nuclear transport of homeodomain proteins during development

Cited by 18 publications

References 145 publications

PITX2: A promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma

PITX2: A promising predictive biomarker of patients' prognosis and chemoradioresistance in esophageal squamous cell carcinoma

Automated Quantification of the Subcellular Localization of Multicompartment Proteins via Q‐SCAn

Nuclear localization of Obox4 is dependent on its homeobox domain

Contact Info

Product

Resources

About