← Back to Search
Drosophila Ste-20 Family Protein Kinase, Hippo, Modulates Fat Cell Proliferation
Hongling Huang, W. Wu, L. Zhang, X. Liu
Published 2013 · Medicine, Biology
Save to my Library
Download PDFAnalyze on Scholarcy
Background Evolutionarily conserved Hippo (Hpo) pathway plays a pivotal role in the control of organ size. Although the Hpo pathway regulates proliferation of a variety of epidermal cells, its function in non-ectoderm-derived cells is largely unknown. Methodology/Principal Findings Through methods including fat quantification assays, starvation assays, in vivo labeling assays, we show that overexpression of Hpo in Drosophila melanogaster fat body restricts Drosophila body growth and reduces fat storage through regulation of adipocyte proliferation rather than through influencing the size of fat cells and lipid metabolism, whereas compromising Hpo activity results in weight gain and greater fat storage. Furthermore, we provide evidence that Yorkie (Yki, a transcriptional coactivator that functions in the Hpo pathway) antagonizes Hpo to modulate fat storage in Drosophila. Conclusions/Significance Our findings specify a role of Hpo in controlling mesoderm-derived cell proliferation. The observed anti-obesity effects of Hpo may indicate great potential for its utilization in anti-obesity therapeutics.
This paper references
The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway.
S. Wu (2008)
Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor, Mats
Z. Lai (2005)
Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body
Dae Sung Hwangbo (2004)
Adipose is a conserved dosage-sensitive antiobesity gene.
J. M. Suh (2007)
PTPN14 is required for the density-dependent control of YAP1.
W. Wang (2012)
Drosophila Pez Acts in Hippo Signaling to Restrict Intestinal Stem Cell Proliferation
Ingrid Poernbacher (2012)
Targeting adipocyte apoptosis: a novel strategy for obesity therapy.
Yu Zhang (2012)
Hedgehog signaling plays a conserved role in inhibiting fat formation.
J. M. Suh (2006)
Alzheimer's disease: insights from Drosophila melanogaster models
Aileen Moloney (2010)
Transcription factor choice in the Hippo signaling pathway: homothorax and yorkie regulation of the microRNA bantam in the progenitor domain of the Drosophila eye imaginal disc.
H. Peng (2009)
The Hippo Signaling Pathway Coordinately Regulates Cell Proliferation and Apoptosis by Inactivating Yorkie, the Drosophila Homolog of YAP
J. Huang (2005)
The obesity pipeline: current strategies in the development of anti-obesity drugs
Dunstan Cooke (2006)
cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines
ZC Lai (2005)
Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways
C. Alárcon (2009)
The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control.
L. Zhang (2008)
Obesity, insulin resistance, and cardiovascular disease.
G. Reaven (2004)
Homeodomain-Interacting Protein Kinase Regulates Yorkie Activity to Promote Tissue Growth
J. Chen (2012)
Hid can induce, but is not required for autophagy in polyploid larval Drosophila tissues.
G. Juhász (2005)
The public health impact of obesity.
T. Visscher (2001)
Hippo signaling regulates Drosophila intestine stem cell proliferation through multiple pathways
Fangfang Ren (2010)
Size, number and function of adipose tissue cells in human obesity.
P. Björntorp (1974)
Review Paper: Current Strategies in the Development of Anti-obesity Drugs and Their Safety Concerns
C. Elangbam (2009)
Fat‐body remodeling in Drosophila melanogaster
Archana Nelliot (2006)
Insect fat body: energy, metabolism, and regulation.
E. L. Arrese (2010)
A Drosophila model of Parkinson's disease
M. Feany (2000)
Mammalian Hippo pathway: from development to cancer and beyond.
Yijun Bao (2011)
Dimerization and Cytoplasmic Localization Regulate Hippo Kinase Signaling Activity in Organ Size Control*
Yunyun Jin (2012)
Embryonic fat-cell lineage in Drosophila melanogaster.
D. Hoshizaki (1994)
The Drosophila Ste20 family kinase dMST functions as a tumor suppressor by restricting cell proliferation and promoting apoptosis.
J. Jia (2003)
The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration
P. Karpowicz (2010)
Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase.
T. Xu (1995)
Molecular regulation of adipogenesis.
E. Rosen (2000)
proliferation and promotes apoptosis
S Wu (2003)
Diet-induced adipocyte number increase in adult rats: a new model of obesity.
I. Faust (1978)
Promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines
N Tapon (2002)
Brummer lipase is an evolutionary conserved fat storage regulator in Drosophila.
Sebastian Grönke (2005)
The Drosophila Mst Ortholog, hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis
K. Harvey (2003)
The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation.
R. Justice (1995)
The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal
B. Zhao (2011)
Hippo Pathway Inhibits Wnt Signaling to Restrain Cardiomyocyte Proliferation and Heart Size
Todd R. Heallen (2011)
Fly models of Huntington's disease.
J. Marsh (2003)
salvador Promotes Both Cell Cycle Exit and Apoptosis in Drosophila and Is Mutated in Human Cancer Cell Lines
N. Tapon (2002)
Cell number and size as a determinant of subsequent obesity.
J. Hirsch (1975)
Cooperative control of Drosophila immune responses by the JNK and NF‐κB signaling pathways
Joseph R. Delaney (2006)
The hippo signaling pathway in development and cancer.
D. Pan (2010)
The cell adhesion molecule echinoid functions as a tumor suppressor and upstream regulator of the Hippo signaling pathway.
Tao Yue (2012)
National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants
Mariel M. Finucane (2011)
Direct Induction of Autophagy by Atg1 Inhibits Cell Growth and Induces Apoptotic Cell Death
R. C. Scott (2007)
hippo Encodes a Ste-20 Family Protein Kinase that Restricts Cell Proliferation and Promotes Apoptosis in Conjunction with salvador and warts
Shian Wu (2003)
This paper is referenced by
The Hippo Signaling Transducer TAZ Regulates Mammary Gland Morphogenesis and Carcinogen-induced Mammary Tumorigenesis
Kayla E. Denson (2018)
Measuring the Kinase Activity of GCKIII Proteins In Vitro.
J. Zalvide (2020)
YAP1 regulates PPARG and RXR alpha expression to affect the proliferation and differentiation of ovine preadipocyte
Kaiping Deng (2019)
An in vivo RNAi screen identifies evolutionary conserved Drosophila fat storage regulators.
J. Baumbach (2014)
MST Kinases and Metabolism.
C. Pombo (2019)
Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism
A. Ardestani (2018)
Integration of Hippo-YAP Signaling with Metabolism.
C. Ibar (2020)
KRAS, YAP, and obesity in pancreatic cancer: A signaling network with multiple loops.
G. Eibl (2019)