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Tumor Suppressor Pa...
Tumor Suppressor Par-4 Regulates Complement Factor C3 and Obesity
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- Araujo, Nathalia (author)
- University of Kentucky
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- Sledziona, James (author)
- University of Kentucky
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- Noothi, Sunil K. (author)
- University of Kentucky
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- Burikhanov, Ravshan (author)
- University of Kentucky
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- Hebbar, Nikhil (author)
- University of Kentucky
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- Ganguly, Saptadwipa (author)
- University of Kentucky
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- Shrestha-Bhattarai, Tripti (author)
- Memorial Sloan-Kettering Cancer Center
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- Zhu, Beibei (author)
- University of Kentucky
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- Katz, Wendy S. (author)
- University of Kentucky
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- Zhang, Yi (author)
- University of Kentucky
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- Taylor, Barry S. (author)
- Memorial Sloan-Kettering Cancer Center
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- Liu, Jinze (author)
- University of Kentucky
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- Chen, Li (author)
- University of Kentucky Medical Center,University of Kentucky
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- Weiss, Heidi L. (author)
- University of Kentucky Medical Center,University of Kentucky
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- He, Daheng (author)
- University of Kentucky
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- Wang, Chi (author)
- University of Kentucky Medical Center,University of Kentucky
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- Morris, Andrew J. (author)
- University of Kentucky,University of Kentucky Medical Center
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- Cassis, Lisa A. (author)
- University of Kentucky
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- Nikolova-Karakashian, Mariana (author)
- University of Kentucky,University of Kentucky Medical Center
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- Nagareddy, Prabhakar R. (author)
- Ohio State University
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- Melander, Olle (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital
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- Evers, B. Mark (author)
- University of Kentucky Medical Center,University of Kentucky
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- Kern, Philip A. (author)
- University of Kentucky
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- Rangnekar, Vivek M. (author)
- University of Kentucky,University of Kentucky Medical Center
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(creator_code:org_t)
- 2022-03-29
- 2022
- English.
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In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12
- Related links:
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Abstract
Subject headings
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- Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed the obese mouse phenotype. Moreover, obese human subjects showed lower expression of Par-4 relative to lean subjects, and in longitudinal studies, low baseline Par-4 levels denoted an increased risk of developing obesity later in life. These findings indicate that Par-4 suppresses p53 and its target c3 to regulate obesity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- acylation stimulating protein
- adipocyte tissue storage
- C3
- fat absorption
- hypertrophic obesity
- Par-4
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Araujo, Nathalia
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Sledziona, James
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Noothi, Sunil K.
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Burikhanov, Ravs ...
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Hebbar, Nikhil
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Ganguly, Saptadw ...
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show more...
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Shrestha-Bhattar ...
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Zhu, Beibei
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Katz, Wendy S.
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Zhang, Yi
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Taylor, Barry S.
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Liu, Jinze
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Chen, Li
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Weiss, Heidi L.
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He, Daheng
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Wang, Chi
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Morris, Andrew J ...
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Cassis, Lisa A.
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Nikolova-Karakas ...
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Nagareddy, Prabh ...
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Melander, Olle
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Evers, B. Mark
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Kern, Philip A.
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Rangnekar, Vivek ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Frontiers in Onc ...
- By the university
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Lund University