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Dr. Saja Fakhraldeen
Kuwait Institute for Scientific Research

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0 Biological Engineering
0 Microbiology
0 Biochemistry and Cell Biology
0 pathology, oncology
0 Cellular and Molecular Biology

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Preprint content
Published: 10 June 2021
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RNA binding proteins (RBPs) regulate expression of large cohorts of RNA species to affect programmatic changes in cellular phenotypes. In order to describe the function of RBPs within a cell, it is key to identify their mRNA binding partners. This is often done by cross-linking nucleic acids to RBPs, followed by chemical release of the nucleic acid fragments for analysis. However, this methodology is lengthy, involves complex processing leading to extraordinary losses, requires large amounts of starting materials, and is prone to artifacts due to the labile nature of mRNA. To evaluate potential alternative technologies, we tested "exclusion-based" purification of immunoprecipitates (oil-based IFAST™ or air-based SLIDE™), and report here that these methods can efficiently, rapidly and specifically isolate RBP-RNA complexes with minimal handling. The analysis starts with >100x less material than for techniques that include cross-linking. Depending on the specific antibody used, 50-100% of starting protein is retrieved, allowing the assay of endogenous levels of RBP instead of tagged and over-expressed ectopic proteins. Isolated protein and nucleic acid components are purified and analyzed using standard techniques to provide a comprehensive portrait of RBP complexes. Using exclusion-based techniques, we show that the mRNA binding partners for CRD-BP/IMP1/IGF2BP1/ZBP1 in cultured mammary epithelial cells are enriched in mRNAs important for de-toxifying superoxides (glutathione metabolic enzymes) and other mRNAs encoding mitochondrial proteins.

ACS Style

Saja A. Fakhraldeen; Scott M. Berry; David J. Beebe; Avtar A Roopra; Vladimir S. Spiegelman; Caroline M. Alexander. Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells. 2021, 1 .

AMA Style

Saja A. Fakhraldeen, Scott M. Berry, David J. Beebe, Avtar A Roopra, Vladimir S. Spiegelman, Caroline M. Alexander. Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells. . 2021; ():1.

Chicago/Turabian Style

Saja A. Fakhraldeen; Scott M. Berry; David J. Beebe; Avtar A Roopra; Vladimir S. Spiegelman; Caroline M. Alexander. 2021. "Enhanced Immunoprecipitation Techniques for the Identification of RNA Binding Protein Partners: CRD-BP interactions in mammary epithelial cells." , no. : 1.

Journal article
Published: 11 September 2020 in Sustainability
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The research and development (R&D) expenditure in Kuwait is insufficient to lead to innovation and a knowledge economy. Investment in R&D has been shown to sustain elevated economic performance. The objective of this study is to explore the association between three competing dimensions of R&D indicators that lead to sustainable economic performance within any given country, namely, R&D expenditure, the number of researchers, and the number of patent rights, using time-series data collected over a 20-year period (1996–2016) by the World Bank Group. R&D indicators were compared between high- and middle-income countries including models from Asian (South Korea, Singapore, and Malaysia) and European (Finland and Ireland) countries as well as the State of Kuwait. Moreover, a case study describing R&D investments in Kuwait is presented. Overall, the results reveal higher R&D spending, number of researchers, and gross domestic product (GDP) per capita for the Asian and European models. Current R&D expenditure in Kuwait is estimated at 0.08% of GDP (2016), which is significantly lower than the mean of the middle-income countries (1.58%). Furthermore, the number of researchers (per million) in Kuwait (386) is less than half of the mean number of researchers in middle-income countries (775) (2015). Low R&D investments in the State of Kuwait has gradually led to a decreased GDP per capita. Regression analysis shows that GDP per capita can be predicted solely based on the number of researchers (beta = 0.780, R2 = 0.608). The number of researchers is the most crucial variable to predict GDP per capita, and the R&D expenditure is a good indicator of the number of researchers. These findings offer invaluable insight into the sustainable development goals (SDG 9). To our knowledge, this paper presents the first application of the effect of R&D on sustainable economic performance with reference to the SDG target 9.5 “Research & Development”. Thus, in order to enhance scientific research (both academic, professional, and industrial), countries need to increase the number of researchers, and these actions are necessary to introduce sustainable growth to GDP.

ACS Style

Ahmad Salman; Ali Al-Hemoud; Saja Fakhraldeen; Maha Al-Nashmi; Suad AlFadhli; Sungsoo Chun. Research and Development as a Moderating Variable for Sustainable Economic Performance: The Asian, European, and Kuwaiti Models. Sustainability 2020, 12, 7525 .

AMA Style

Ahmad Salman, Ali Al-Hemoud, Saja Fakhraldeen, Maha Al-Nashmi, Suad AlFadhli, Sungsoo Chun. Research and Development as a Moderating Variable for Sustainable Economic Performance: The Asian, European, and Kuwaiti Models. Sustainability. 2020; 12 (18):7525.

Chicago/Turabian Style

Ahmad Salman; Ali Al-Hemoud; Saja Fakhraldeen; Maha Al-Nashmi; Suad AlFadhli; Sungsoo Chun. 2020. "Research and Development as a Moderating Variable for Sustainable Economic Performance: The Asian, European, and Kuwaiti Models." Sustainability 12, no. 18: 7525.

Commentary
Published: 12 August 2020 in Healthcare
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Kuwait Vision 2035 is an initiative that was launched in 2017 by His Highness the Emir of the State of Kuwait Sheikh Sabah Al-Ahmad Al-Jaber Al-Sabah. This initiative includes the implementation of a detailed development plan aimed at transforming the state of Kuwait into a regional leader in science, technology, and innovation. Health research will arguably prove to be one of the most impactful research arenas when it comes to accomplishing the goals set forth by the Kuwait Vision 2035 Development Plan. The high impact of health research is derived from its capacity to aid in the establishment of a knowledge-based health industry. The state of Kuwait lacks a system for promoting and managing national R&D efforts. At present, the research and development (R&D) expenditure in the state of Kuwait is far below the international standards that have been shown to lead to innovation and the subsequent development of a knowledge-based economy. Improvement of the weak and unstructured existing R&D apparatus in the State of Kuwait is among the most urgent challenges facing the nation as it strives toward innovation and development of a knowledge-based economy. Developing health research capacities in the State of Kuwait can significantly contribute toward improving public health, health promotion, disease prevention and treatment, and overall human welfare. Importantly, the positive impacts of such extensive benefits will not be restricted to the state of Kuwait and its citizens, but may in fact reap benefits for the global society as a whole. This article first analyzes the current status of healthcare services and health science research in the State of Kuwait, and then summarizes some essential R&D design principles that Kuwait needs to implement in order to achieve the milestones set forth in the Kuwait Vision 2035 Development Plan.

ACS Style

Ahmad Salman; Saja Fakhraldeen; Sungsoo Chun; Kazi Jamil; Janvier Gasana; Adel Al-Hunayan. Enhancing Research and Development in the Health Sciences as a Strategy to Establish a Knowledge-Based Economy in the State of Kuwait: A Call for Action. Healthcare 2020, 8, 264 .

AMA Style

Ahmad Salman, Saja Fakhraldeen, Sungsoo Chun, Kazi Jamil, Janvier Gasana, Adel Al-Hunayan. Enhancing Research and Development in the Health Sciences as a Strategy to Establish a Knowledge-Based Economy in the State of Kuwait: A Call for Action. Healthcare. 2020; 8 (3):264.

Chicago/Turabian Style

Ahmad Salman; Saja Fakhraldeen; Sungsoo Chun; Kazi Jamil; Janvier Gasana; Adel Al-Hunayan. 2020. "Enhancing Research and Development in the Health Sciences as a Strategy to Establish a Knowledge-Based Economy in the State of Kuwait: A Call for Action." Healthcare 8, no. 3: 264.

Article
Published: 05 September 2019 in Environmental Biology of Fishes
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Brown algae comprise the largest biomass producers in coastal waters and play important ecological roles. The complex nature of cell wall polysaccharides limits the extraction of bioactive compounds from these seaweeds. The aim of the study was to use enzyme-assisted extraction as a tool to release the bioactive compounds from seven brown seaweeds of Kuwait coast and characterization of the active extracts. The enzymatic extracts obtained by hydrolysing seaweeds with five carbohydrases and three proteases were screened for antioxidant and antimicrobial activity. Yield, total phenolics, and bioactivity were as a function of species difference in cell wall composition and specificity of the enzyme used. Among the six species of brown seaweeds studied, the enzymatic extracts obtained from Sargassum boveanum, Sargassum angustifolium, and Feldmannia irregularis showed high antioxidant activity in different assays. Though antimicrobial activities of the enzymatic extracts were low, Flavourzyme resulted in more number of seaweed extracts with antimicrobial activity against foodborne pathogens. In general, carbohydrases resulted in extracts with high radical scavenging activity whereas proteases resulted in extracts with high iron chelating activity. The extracts with highest antioxidant activity such as S. boveanum-Viscozyme and Alcalase extracts were further fractionated and characterized. The polyphenol and polysaccharide-rich fractions were responsible for the high radical scavenging and reducing power whereas the iron chelating activity and inhibition of lipid oxidation in liposome model system was mainly contributed by polysaccharide and protein-rich fractions. The results of study showed that enzyme-assisted extraction could be useful to make tailor-made seaweed extracts with specific bioactivity.

ACS Style

Sabeena Farvin K. Habeebullah; Surendraraj Alagarsamy; Zainab Sattari; Sakinah Al-Haddad; Saja Fakhraldeen; Aws Al-Ghunaim; Faiza Al-Yamani. Enzyme-assisted extraction of bioactive compounds from brown seaweeds and characterization. Environmental Biology of Fishes 2019, 32, 615 -629.

AMA Style

Sabeena Farvin K. Habeebullah, Surendraraj Alagarsamy, Zainab Sattari, Sakinah Al-Haddad, Saja Fakhraldeen, Aws Al-Ghunaim, Faiza Al-Yamani. Enzyme-assisted extraction of bioactive compounds from brown seaweeds and characterization. Environmental Biology of Fishes. 2019; 32 (1):615-629.

Chicago/Turabian Style

Sabeena Farvin K. Habeebullah; Surendraraj Alagarsamy; Zainab Sattari; Sakinah Al-Haddad; Saja Fakhraldeen; Aws Al-Ghunaim; Faiza Al-Yamani. 2019. "Enzyme-assisted extraction of bioactive compounds from brown seaweeds and characterization." Environmental Biology of Fishes 32, no. 1: 615-629.

Original article
Published: 30 May 2019 in Letters in Applied Microbiology
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In this study, a total of 172 putative omega-3 producers were isolated from 28 sediment samples from the Arabian Gulf employing a selective isolation procedure using marine agar containing 0·1% triphenyl tetrazolium chloride (TTC). Out of these 172 isolates, 19 isolates produced eicosapentaenoic acid (EPA) as confirmed by Gas Chromatography-Mass Spectrometry (GC-MS). The EPA content of the isolated bacterial strain varied from 1·76 to 6·52% of total fatty acids. Among the 19 isolates of EPA producers, while 17 isolates harboured both pfaA gene and Δ6 desaturase gene, only five isolates harboured Δ5 desaturase gene. Two of the EPA positive strains harbour none of the three genes tested. The 16s RNA identification of these isolates revealed that except one, all the EPA producers were Gram-positive marine bacteria belonging to the phylum Firmicutes, family Bacillacea, genera Bacillus and Oceanobacillus. Halomonas pacifica was the only Gram-negative Gamma-Proteobacteria detected to produce EPA from this region. SIGNIFICANCE AND IMPACT OF THE STUDY: Recently, marine bacteria are considered as a promising source of polyunsaturated fatty acid (PUFA) over marine fishes and microalgae. PUFA producers reported from polar and deep-sea sources were restricted to five well-known marine genera under two distinct domains of bacteria such as proteobacteria (Shewanella, Colwellia, and Moritella) and cytophaga group (Flexibacter, Psychroflexus). This study revealed that subtropical marine environment could also be the source of PUFA producing bacteria, and they predominantly belonged to the class of Firmibacteria. This finding opens up new avenue for research to study the inherent mechanism and physiology of such organisms from this unique environment.

ACS Style

Surendraraj Alagarsamy; K.H. Sabeena Farvin; Saja Fakhraldeen; Meera Regu Kooramattom; Faiza Al‐Yamani; Sabeena Farvin; K.H. Saja Fakhraldeen. Isolation of Gram‐positiveFirmibacteriaas major eicosapentaenoic acid producers from subtropical marine sediments. Letters in Applied Microbiology 2019, 69, 121 -127.

AMA Style

Surendraraj Alagarsamy, K.H. Sabeena Farvin, Saja Fakhraldeen, Meera Regu Kooramattom, Faiza Al‐Yamani, Sabeena Farvin, K.H. Saja Fakhraldeen. Isolation of Gram‐positiveFirmibacteriaas major eicosapentaenoic acid producers from subtropical marine sediments. Letters in Applied Microbiology. 2019; 69 (2):121-127.

Chicago/Turabian Style

Surendraraj Alagarsamy; K.H. Sabeena Farvin; Saja Fakhraldeen; Meera Regu Kooramattom; Faiza Al‐Yamani; Sabeena Farvin; K.H. Saja Fakhraldeen. 2019. "Isolation of Gram‐positiveFirmibacteriaas major eicosapentaenoic acid producers from subtropical marine sediments." Letters in Applied Microbiology 69, no. 2: 121-127.

Other
Published: 23 January 2018 in Cancer Research
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Although anti-estrogen therapies are successful in many patients with estrogen receptor alpha-positive (ERα+) breast cancer, 25-40% fail to respond. Although multiple mechanisms underlie evasion of these treatments, including tumor heterogeneity and drug-resistant cancer stem cells (CSCs), further investigations have been limited by the paucity of preclinical ERα+ tumor models. Here we examined a mouse model of prolactin-induced aggressive ERα+ breast cancer, which mimics the epidemiologic link between prolactin exposure and increased risk for metastatic ERα+ tumors. Like a subset of ERα+ patient cancers, the prolactin-induced adenocarcinomas contained two major tumor subpopulations that expressed markers of normal luminal and basal epithelial cells. CSC activity was distributed equally across these two tumor subpopulations. Treatment with the selective estrogen receptor downregulator (SERD), ICI 182,780 (ICI), did not slow tumor growth, but induced adaptive responses in CSC activity, increased markers of plasticity including target gene reporters of Wnt/Notch signaling and epithelial-mesenchymal transition, and increased double positive (K8/K5) cells. In primary tumorsphere cultures, ICI stimulated CSC self-renewal, and was able to overcome the dependence of self-renewal upon Wnt or Notch signaling individually, but not together. Our findings demonstrate that treatment of aggressive mixed lineage ERα+ breast cancers with a SERD does not inhibit growth, but rather evokes tumor cell plasticity and regenerative CSC activity, predicting likely negative impacts on patient tumors with these characteristics.

ACS Style

Michael P. Shea; Kathleen A. O'leary; Saja Fakhraldeen; Vincent Goffin; Andreas Friedl; Kari B. Wisinski; Caroline M. Alexander; Linda A. Schuler. Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα+ Mammary Carcinomas. Cancer Research 2018, 78, 1672 -1684.

AMA Style

Michael P. Shea, Kathleen A. O'leary, Saja Fakhraldeen, Vincent Goffin, Andreas Friedl, Kari B. Wisinski, Caroline M. Alexander, Linda A. Schuler. Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα+ Mammary Carcinomas. Cancer Research. 2018; 78 (7):1672-1684.

Chicago/Turabian Style

Michael P. Shea; Kathleen A. O'leary; Saja Fakhraldeen; Vincent Goffin; Andreas Friedl; Kari B. Wisinski; Caroline M. Alexander; Linda A. Schuler. 2018. "Antiestrogen Therapy Increases Plasticity and Cancer Stemness of Prolactin-Induced ERα+ Mammary Carcinomas." Cancer Research 78, no. 7: 1672-1684.

Journal article
Published: 15 March 2016 in Molecular and Cellular Biology
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Lrp5 is typically described as a Wnt signaling receptor, albeit a less effective Wnt signaling receptor than the better-studied sister isoform, Lrp6. Here we show that Lrp5 is only a minor player in the response to Wnt3a-type ligands in mammary epithelial cells; instead, Lrp5 is required for glucose uptake, and glucose uptake regulates the growth rate of mammary epithelial cells in culture. Thus, a loss of Lrp5 leads to profound growth suppression, whether growth is induced by serum or by specific growth factors, and this inhibition is not due to a loss of Wnt signaling. Depletion of Lrp5 decreases glucose uptake, lactate secretion, and oxygen consumption rates; inhibition of glucose consumption phenocopies the loss of Lrp5 function. Both Lrp5 knockdown and low external glucose induce mitochondrial stress, as revealed by the accumulation of reactive oxygen species (ROS) and the activation of the ROS-sensitive checkpoint, p38α. In contrast, loss of function of Lrp6 reduces Wnt responsiveness but has little impact on growth. This highlights the distinct functions of these two Lrp receptors and an important Wnt ligand-independent role of Lrp5 in glucose uptake in mammary epithelial cells.

ACS Style

Emily N. Chin; Joshua A. Martin; Soyoung Kim; Saja A. Fakhraldeen; Caroline M. Alexander. Lrp5 Has a Wnt-Independent Role in Glucose Uptake and Growth for Mammary Epithelial Cells. Molecular and Cellular Biology 2016, 36, 871 -885.

AMA Style

Emily N. Chin, Joshua A. Martin, Soyoung Kim, Saja A. Fakhraldeen, Caroline M. Alexander. Lrp5 Has a Wnt-Independent Role in Glucose Uptake and Growth for Mammary Epithelial Cells. Molecular and Cellular Biology. 2016; 36 (6):871-885.

Chicago/Turabian Style

Emily N. Chin; Joshua A. Martin; Soyoung Kim; Saja A. Fakhraldeen; Caroline M. Alexander. 2016. "Lrp5 Has a Wnt-Independent Role in Glucose Uptake and Growth for Mammary Epithelial Cells." Molecular and Cellular Biology 36, no. 6: 871-885.

Journal article
Published: 01 May 2015 in Journal of Biological Chemistry
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CRD-BP/IGF2BP1 has been characterized as an "oncofetal" RNA binding protein typically highly expressed in embryonic tissues, suppressed in normal adult tissues, but induced in many tumor types. In this study, we show that adult breast tissues express ubiquitous but low levels of CRD-BP protein and mRNA. Although CRD-BP mRNA expression is induced in breast tumor cells, levels remain ∼1000-fold lower than in embryonic tissues. Despite low expression levels, CRD-BP is required for clonogenic growth of breast cancer cells. We reveal that because the most common protein isoform in normal adult breast and breast tumors has an N-terminal deletion (lacking two RNA recognition motif (RRM) domains) and is therefore missing antibody epitopes, CRD-BP expression has been under-reported by previous studies. We show that a CRD-BP mutant mouse strain retains expression of the shorter transcript (ΔN-CRD-BP), which originates in intron 2, suggesting that the impact of complete ablation of this gene in mice is not yet known. Either the full-length CRD-BP or the N-terminally truncated version can rescue the clonogenicity of CRD-BP knockdown breast cancer cells, suggesting that clonogenic function is served by either CRD-BP isoform. In summary, although CRD-BP expression levels are low in breast cancer cells, this protein is necessary for clonogenic activity.

ACS Style

Saja A. Fakhraldeen; Rod J. Clark; Avtar Roopra; Emily N. Chin; Wei Huang; John Castorino; Kari B. Wisinski; Taewon Kim; Vladimir S. Spiegelman; Caroline M. Alexander. Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells. Journal of Biological Chemistry 2015, 290, 13386 -13400.

AMA Style

Saja A. Fakhraldeen, Rod J. Clark, Avtar Roopra, Emily N. Chin, Wei Huang, John Castorino, Kari B. Wisinski, Taewon Kim, Vladimir S. Spiegelman, Caroline M. Alexander. Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells. Journal of Biological Chemistry. 2015; 290 (21):13386-13400.

Chicago/Turabian Style

Saja A. Fakhraldeen; Rod J. Clark; Avtar Roopra; Emily N. Chin; Wei Huang; John Castorino; Kari B. Wisinski; Taewon Kim; Vladimir S. Spiegelman; Caroline M. Alexander. 2015. "Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells." Journal of Biological Chemistry 290, no. 21: 13386-13400.

Review
Published: 01 June 2012 in Cold Spring Harbor Perspectives in Biology
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The mouse mammary gland is an outstanding developmental model that exemplifies the activities of many of the effector pathways known to organize mammalian morphogenesis; furthermore, there are well-characterized methods for the specific genetic manipulation of various mammary epithelial cell components. Among these signaling pathways, Wnt signaling has been shown to generate plasticity of fate determination, expanding the genetic programs available to cells in the mammary lineage. It is responsible first for the appearance of the mammary fate in embryonic ectoderm and then for maintaining bi-potential basal stem cells in adult mammary ductal trees. Recent technical developments have led to the separate analysis of various mammary epithelial cell subpopulations, spurring the investigation of Wnt-dependent interactions. Although Wnt signaling was shown to be oncogenic for mouse mammary epithelium even before being identified as the principle oncogenic driver for gut epithelium, conclusive data implicating this pathway as a tumor driver for breast cancer lag behind, and we examine potential reasons.

ACS Style

Caroline M. Alexander; Shruti Goel; Saja Fakhraldeen; Soyoung Kim. Wnt Signaling in Mammary Glands: Plastic Cell Fates and Combinatorial Signaling. Cold Spring Harbor Perspectives in Biology 2012, 4, a008037 -a008037.

AMA Style

Caroline M. Alexander, Shruti Goel, Saja Fakhraldeen, Soyoung Kim. Wnt Signaling in Mammary Glands: Plastic Cell Fates and Combinatorial Signaling. Cold Spring Harbor Perspectives in Biology. 2012; 4 (10):a008037-a008037.

Chicago/Turabian Style

Caroline M. Alexander; Shruti Goel; Saja Fakhraldeen; Soyoung Kim. 2012. "Wnt Signaling in Mammary Glands: Plastic Cell Fates and Combinatorial Signaling." Cold Spring Harbor Perspectives in Biology 4, no. 10: a008037-a008037.

Journal article
Published: 01 May 2012 in Journal of Biological Chemistry
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A canonical Wnt signal maintains adult mammary ductal stem cell activity, and this signal requires the Wnt signaling reception, LRP5. However, previous data from our laboratory have shown that LRP5 and LRP6 are co-expressed in mammary basal cells and that LRP6 is active, leading us to question why LRP6 is insufficient to mediate canonical signaling in the absence of LRP5. Here, we show that at endogenous levels of LRP5 and LRP6 both receptors are required to signal in response to some Wnt ligands both in vitro (in mouse embryonic fibroblasts and mammary epithelial cells) and in vivo (in mammary outgrowths). This subgroup of canonical ligands includes Wnt1, Wnt9b, and Wnt10b; the latter two are expressed in mammary gland. In contrast, the ligand commonly used experimentally, Wnt3a, prefers LRP6 and requires just one receptor regardless of cellular context. When either LRP5 or LRP6 is overexpressed, signaling remains ligand-dependent, but the requirement for both receptors is abrogated (regardless of ligand type). We have documented an LRP5-6 heteromer using immiscible filtration assisted by surface tension (IFAST) immunoprecipitation. Together, our data imply that under physiological conditions some Wnt ligands require both receptors to be present to generate a canonical signal. We have designed a model to explain our results based on the resistance of LRP5-6 heteromers to a selective inhibitor of E1/2-binding Wnt-LRP6 interaction. These data have implications for stem cell biology and for the analysis of the oncogenicity of LRP receptors that are often overexpressed in breast tumors.

ACS Style

Shruti Goel; Emily N. Chin; Saja A. Fakhraldeen; Scott M. Berry; David J. Beebe; Caroline M. Alexander. Both LRP5 and LRP6 Receptors Are Required to Respond to Physiological Wnt Ligands in Mammary Epithelial Cells and Fibroblasts. Journal of Biological Chemistry 2012, 287, 16454 -16466.

AMA Style

Shruti Goel, Emily N. Chin, Saja A. Fakhraldeen, Scott M. Berry, David J. Beebe, Caroline M. Alexander. Both LRP5 and LRP6 Receptors Are Required to Respond to Physiological Wnt Ligands in Mammary Epithelial Cells and Fibroblasts. Journal of Biological Chemistry. 2012; 287 (20):16454-16466.

Chicago/Turabian Style

Shruti Goel; Emily N. Chin; Saja A. Fakhraldeen; Scott M. Berry; David J. Beebe; Caroline M. Alexander. 2012. "Both LRP5 and LRP6 Receptors Are Required to Respond to Physiological Wnt Ligands in Mammary Epithelial Cells and Fibroblasts." Journal of Biological Chemistry 287, no. 20: 16454-16466.

Short communication
Published: 10 December 2011 in DNA Repair
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The tumor suppressor p53 is a transcription factor whose function is critical for maintaining genomic stability in mammalian cells. In response to DNA damage, p53 initiates a signaling cascade that results in cell cycle arrest, DNA repair or, if the damage is severe, programmed cell death. In addition, p53 interacts with repair proteins involved in homologous recombination. Mitotic homologous recombination (HR) plays an essential role in the repair of double-strand breaks (DSBs) and broken replication forks. Loss of function of either p53 or HR leads to an increased risk of cancer. Given the importance of both p53 and HR in maintaining genomic integrity, we analyzed the effect of p53 on HR in vivo using Fluorescent Yellow Direct Repeat (FYDR) mice as well as with the sister chromatid exchange (SCE) assay. FYDR mice carry a direct repeat substrate in which an HR event can yield a fluorescent phenotype. Here, we show that p53 status does not significantly affect spontaneous HR in adult pancreatic cells in vivo or in primary fibroblasts in vitro when assessed using the FYDR substrate and SCEs. In addition, primary fibroblasts from p53 null mice do not show increased susceptibility to DNA damage-induced HR when challenged with mitomycin C. Taken together, the FYDR assay and SCE analysis indicate that, for some tissues and cell types, p53 status does not greatly impact HR.

ACS Style

Dominika M. Wiktor-Brown; Michelle R. Sukup-Jackson; Saja Fakhraldeen; Carrie A. Hendricks; Bevin P. Engelward. p53 null Fluorescent Yellow Direct Repeat (FYDR) mice have normal levels of homologous recombination. DNA Repair 2011, 10, 1294 -1299.

AMA Style

Dominika M. Wiktor-Brown, Michelle R. Sukup-Jackson, Saja Fakhraldeen, Carrie A. Hendricks, Bevin P. Engelward. p53 null Fluorescent Yellow Direct Repeat (FYDR) mice have normal levels of homologous recombination. DNA Repair. 2011; 10 (12):1294-1299.

Chicago/Turabian Style

Dominika M. Wiktor-Brown; Michelle R. Sukup-Jackson; Saja Fakhraldeen; Carrie A. Hendricks; Bevin P. Engelward. 2011. "p53 null Fluorescent Yellow Direct Repeat (FYDR) mice have normal levels of homologous recombination." DNA Repair 10, no. 12: 1294-1299.