Lipid droplet and milk lipid globule membrane associated placental protein 17b (PP17b) is involved in apoptotic and differentiation processes of human epithelial cervical carcinoma cells.
The intracellular role of placental protein 17b (PP17b)/TIP47 has been controversial, because it is considered to be a protein required for mannose 6-phosphate receptor transport from endosome to trans-Golgi as well as a neutral lipid droplet-associated protein. The similarity between the amino acid sequences of PP17 variants, adipophilin and perilipins, and between their gene structures indicate that PP17b as well as other alternatively spliced PP17 variants belong to the lipid storage droplet protein family, containing also some differentiation factors. Using a specific antibody, PP17b was detected in lipid droplet fractions and co-localized with neutral lipid droplets stained by Nile red, and fluorescently labelled PP17 antibody in HeLa cells with confocal microscopy. PP17b was also detected in milk, associated to milk lipid globule membranes. Cytostatic agents induced apoptosis and PP17b synthesis in HeLa cells, which was significantly inhibited by protein kinase C (PKC) inhibitor, indicating the involvement of NF-kappa B and AP-1 transcription factors in this process, while protein kinase A (PKA) inhibitor had only a modest inhibitory effect. Cell differentiation induced by dibutyryl cyclic AMP or phorbol myristate acetate also increased PP17b synthesis, demonstrating its strong involvement in cell differentiation. PP17b synthesis was higher in M than in G0/G1 phases in control, apoptotic and differentiated cells. This data shows that PP17b is a neutral lipid droplet-associated protein, and its expression is regulated by PKC- and PKA-dependent pathways.
Than
Nandor G
NG
First Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary.
Sumegi
Balazs
B
Bellyei
Szabolcs
S
Berki
Timea
T
Szekeres
Gyorgy
G
Janaky
Tamas
T
Szigeti
Andras
A
Bohn
Hans
H
Than
Gabor N
GN
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000378:metabolism; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002458:Cell Fractionation; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006017:Glycolipids / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D066292:Lipid Droplets; D050356:Lipid Metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000070796:Perilipin-3; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D016415:Sequence Alignment; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology; D033921:Vesicular Transport Proteins
D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006017:Glycolipids; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; C038196:PLIN3 protein, human; D010446:Peptide Fragments; D000070796:Perilipin-3; D011257:Pregnancy Proteins; D020033:Protein Isoforms; D033921:Vesicular Transport Proteins; C110367:milk fat globule; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C