المؤلفون: McDermott, Jason E., Jacobs, Jon M., Merrill, Nathaniel J., Mitchell, Hugh D., Arshad, Osama A., McClure, Ryan, Teeguarden, Justin, Gajula, Rajendra P., Porter, Kenneth I., Satterfield, Brieann C., Lundholm, Kirsie R., Skene, Debra J., Gaddameedhi, Shobhan, Dongen, Hans P. A. Van

المصدر: Journal of Proteome Research; 5/3/2024, Vol. 23 Issue 5, p1547-1558, 12p

المؤلفون: Skene, Debra J., Skornyakov, Elena, Chowdhury, Namrata R., Gajula, Rajendra P., Middleton, Benita, Satterfield, Brieann C., Porter, Kenneth I., Van Dongen, Hans P. A., Gaddameedhi, Shobhan

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2018 Jul . 115(30), 7825-7830.

الوصول الحر: https://www.jstor.org/stable/26511292Test

المؤلفون: Skene, Debra, Skornyakov, Elena, Chowdhury, Namrata, Gajula, Rajendra P, Middleton, Benita, Satterfield, Brieann C, Porter, Kenneth I, Van Dongen, Hans P A, Gaddameedhi, Shobhan

الوصف: Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is esse ntial to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock distur- bances may offer new insight s. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-s hift schedule, compared with a simulated day-shift schedule, we re analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhyth- micity under constant routine following either or both simulated shift schedules. However, while tradition al markers of the circadian clock in the SCN — melatonin, cortisol, and PER3 expression — maintained a stable phase alignment after both schedules, only a few metabo- lites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine fol- lowing the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavior- al time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circa- dian clock. Characterization of these metabolite rhythms will pro- vide insight into the underlying mechanisms linking shift work and metabolic disorders

وصف الملف: text

العلاقة: http://epubs.surrey.ac.uk/848748Test/; http://www.pnas.org/content/early/2018/07/09/1801183115/tab-article-infoTest; http://epubs.surrey.ac.uk/848748/1/1801183115.full.pdfTest; http://epubs.surrey.ac.uk/848748/2/pnas.1801183115.sapp.pdfTest; Skene, Debra, Skornyakov, Elena, Chowdhury, Namrata, Gajula, Rajendra P, Middleton, Benita, Satterfield, Brieann C, Porter, Kenneth I, Van Dongen, Hans P A and Gaddameedhi, Shobhan (2018) Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism PNAS, 115 (30). pp. 7825-7830.

الإتاحة: https://doi.org/10.1073/pnas.1801183115Test
http://epubs.surrey.ac.uk/848748/1/1801183115.full.pdfTest
http://epubs.surrey.ac.uk/848748/2/pnas.1801183115.sapp.pdfTest

المؤلفون: Gajula, Rajendra P., Chettiar, Sivarajan T., Williams, Russell D., Nugent, Katriana, Kato, Yoshinori, Wang, Hailun, Malek, Reem, Taparra, Kekoa, Cades, Jessica, Annadanam, Anvesh, Yoon, A.-Rum, Fertig, Elana, Firulli, Beth A., Mazzacurati, Lucia, Burns, Timothy F., Firulli, Anthony B., An, Steven S., Tran, Phuoc T.

المساهمون: Department of Pediatrics, IU School of Medicine

المصدر: Publisher

مصطلحات موضوعية: Basic Helix-Loop-Helix Transcription Factors, metabolism, Nuclear Proteins, Prostatic Neoplasms, Protein Interaction Domains and Motifs, Twist Transcription Factor

الوصف: The TWIST1 gene has diverse roles in development and pathologic diseases such as cancer. TWIST1 is a dimeric basic helix-loop-helix (bHLH) transcription factor existing as TWIST1-TWIST1 or TWIST1-E12/47. TWIST1 partner choice and DNA binding can be influenced during development by phosphorylation of Thr125 and Ser127 of the Thr-Gln-Ser (TQS) motif within the bHLH of TWIST1. The significance of these TWIST1 phosphorylation sites for metastasis is unknown. We created stable isogenic prostate cancer cell lines overexpressing TWIST1 wild-type, phospho-mutants, and tethered versions. We assessed these isogenic lines using assays that mimic stages of cancer metastasis. In vitro assays suggested the phospho-mimetic Twist1-DQD mutation could confer cellular properties associated with pro-metastatic behavior. The hypo-phosphorylation mimic Twist1-AQA mutation displayed reduced pro-metastatic activity compared to wild-type TWIST1 in vitro, suggesting that phosphorylation of the TWIST1 TQS motif was necessary for pro-metastatic functions. In vivo analysis demonstrates that the Twist1-AQA mutation exhibits reduced capacity to contribute to metastasis, whereas the expression of the Twist1-DQD mutation exhibits proficient metastatic potential. Tethered TWIST1-E12 heterodimers phenocopied the Twist1-DQD mutation for many in vitro assays, suggesting that TWIST1 phosphorylation may result in heterodimerization in prostate cancer cells. Lastly, the dual phosphatidylinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) inhibitor BEZ235 strongly attenuated TWIST1-induced migration that was dependent on the TQS motif. TWIST1 TQS phosphorylation state determines the intensity of TWIST1-induced pro-metastatic ability in prostate cancer cells, which may be partly explained mechanistically by TWIST1 dimeric partner choice.

وصف الملف: application/pdf

العلاقة: Neoplasia (New York, N.Y.); Gajula, R. P., Chettiar, S. T., Williams, R. D., Nugent, K., Kato, Y., Wang, H., … Tran, P. T. (2015). Structure-Function Studies of the bHLH Phosphorylation Domain of TWIST1 in Prostate Cancer Cells. Neoplasia (New York, N.Y.), 17(1), 16–31. http://doi.org/10.1016/j.neo.2014.10.009Test; https://hdl.handle.net/1805/9244Test

الإتاحة: https://doi.org/10.1016/j.neo.2014.10.009Test
https://hdl.handle.net/1805/9244Test

المؤلفون: Koritala, Bala S. C., Porter, Kenneth I., Arshad, Osama A., Gajula, Rajendra P., Mitchell, Hugh D., Arman, Tarana, Manjanatha, Mugimane G., Teeguarden, Justin, Van Dongen, Hans P. A., McDermott, Jason E., Gaddameedhi, Shobhan

المساهمون: Washington State University, North Carolina State University, National Institutes of Health

المصدر: Journal of Pineal Research ; volume 70, issue 3 ; ISSN 0742-3098 1600-079X

الوصف: Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. We sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24‐hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.

الإتاحة: https://doi.org/10.1111/jpi.12726Test

المؤلفون: Sarkar, Soumyadeep, Porter, Kenneth I., Dakup, Panshak P., Gajula, Rajendra P., Koritala, Bala S. C., Hylton, Ryan, Kemp, Michael G., Wakamatsu, Kazumasa, Gaddameedhi, Shobhan

المساهمون: U.S. Department of Defense, National Institute of Environmental Health Sciences

المصدر: Pigment Cell & Melanoma Research ; volume 34, issue 5, page 955-965 ; ISSN 1755-1471 1755-148X

الوصف: Solar ultraviolet B radiation (UVB) is one of the leading causes of various skin conditions, including photoaging, sunburn erythema, and melanoma. As a protective response, the skin has inbuilt defense mechanisms, including DNA repair, cell cycle, apoptosis, and melanin synthesis. Though DNA repair, cell cycle, and apoptosis are clock controlled, the circadian mechanisms associated with melanin synthesis are not well understood. Using human melanocytes and melanoma cells under synchronized clock conditions, we observed that the microphthalmia‐associated transcription factor (MITF), a rate‐limiting protein in melanin synthesis, is expressed rhythmically with 24‐hr periodicity in the presence of circadian clock protein, BMAL1. Furthermore, we demonstrated that BMAL1 binds to the promoter region of MITF and transcriptionally regulates its expression, which positively influences melanin synthesis. Finally, we report that an increase in melanin levels due to BMAL1 overexpression protects human melanoma cells from UVB. In conclusion, our studies provide novel insights into the mechanistic role of the circadian clock in melanin synthesis and protection against UVB‐mediated DNA damage and genomic instability.

الإتاحة: https://doi.org/10.1111/pcmr.12998Test

المؤلفون: Dakup, Panshak P., Porter, Kenneth I., Gajula, Rajendra P., Goel, Peeyush N., Cheng, Zhaokang, Gaddameedhi, Shobhan

المساهمون: National Cancer Institute, American Heart Association

المصدر: The FASEB Journal ; volume 34, issue 2, page 3347-3358 ; ISSN 0892-6638 1530-6860

الإتاحة: https://doi.org/10.1096/fj.201901850rrTest

المؤلفون: Wild, Aaron T., Gandhi, Nishant, Chettiar, Sivarajan T., Aziz, Khaled, Gajula, Rajendra P., Williams, Russell D., Kumar, Rachit, Taparra, Kekoa, Zeng, Jing, Cades, Jessica A., Velarde, Esteban, Menon, Siddharth, Geschwind, Jean F., Cosgrove, David, Pawlik, Timothy M., Maitra, Anirban, Wong, John, Hales, Russell K., Torbenson, Michael S., Herman, Joseph M., Tran, Phuoc T.

المساهمون: Chuang, Eric Y.

المصدر: PLoS ONE ; volume 8, issue 6, page e65726 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0065726Test

المؤلفون: Gandhi, Nishant, Wild, Aaron T., Chettiar, Sivarajan T., Aziz, Khaled, Kato, Yoshinori, Gajula, Rajendra P., Williams, Russell D., Cades, Jessica A., Annadanam, Anvesh, Song, Danny, Zhang, Yonggang, Hales, Russell K., Herman, Joseph M., Armour, Elwood, DeWeese, Theodore L., Schaeffer, Edward M., Tran, Phuoc T.

المصدر: Cancer Biology & Therapy ; volume 14, issue 4, page 347-356 ; ISSN 1538-4047 1555-8576

الإتاحة: https://doi.org/10.4161/cbt.23626Test

المؤلفون: Li, Da-Qiang, Nair, Sujit S., Ohshiro, Kazufumi, Kumar, Anupam, Nair, Vasudha S., Pakala, Suresh B., Reddy, Sirigiri Divijendra Natha, Gajula, Rajendra P., Eswaran, Jeyanthy, Aravind, L., Kumar, Rakesh

المصدر: Cell Reports ; volume 2, issue 6, page 1657-1669 ; ISSN 2211-1247

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology

الإتاحة: https://doi.org/10.1016/j.celrep.2012.11.018Test
https://api.elsevier.com/content/article/PII:S2211124712004159?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2211124712004159?httpAccept=text/plainTest