PPAN explained

Suppressor of SWI4 1 homolog is a protein that in humans is encoded by the PPAN gene.^{[1] [2]}

The protein encoded by this gene is an evolutionarily conserved protein similar to yeast SSF1 as well as to the gene product of the Drosophila gene peter pan (PPAN). SSF1 is known to be involved in the second step of mRNA splicing. Both SSF1 and PPAN are essential for cell growth and proliferation. This gene was found to cotranscript with P2RY11/P2Y(11), an immediate downstream gene on the chromosome that encodes an ATP receptor. The chimeric transcripts of this gene and P2RY11 were found to be ubiquitously present and regulated during granulocytic differentiation. Exogenous expression of this gene was reported to reduce the anchorage-independent growth of some tumor cells.^[2]

Although being involved in ribosome biogenesis, human PPAN is not merely localized in nucleoli, but also in mitochondria. Depletion of PPAN provokes apoptosis as observed by increased amounts of p53 and its target gene p21, BAX-driven depolarisation of mitochondria, cytochrome c release as well as caspase-dependent cleavage of PARP.^[3] Recent studies revealed that PPAN participates in the regulation of mitochondrial homeostasis, presumably via modulation of autophagy.^[4] Furthermore, PPAN is required for proper cycling of cells since down regulation of PPAN in cancer cells results in a p53-independent cell cycle arrest.^[5]

One of the introns of PPAN encodes the Small nucleolar RNA SNORD105.^[6]

Further reading

• Communi D, Govaerts C, Parmentier M, Boeynaems JM . Cloning of a human purinergic P2Y receptor coupled to phospholipase C and adenylyl cyclase . The Journal of Biological Chemistry . 272 . 51 . 31969–73 . December 1997 . 9405388 . 10.1074/jbc.272.51.31969 . free .
• Migeon JC, Garfinkel MS, Edgar BA . Cloning and characterization of peter pan, a novel Drosophila gene required for larval growth . Molecular Biology of the Cell . 10 . 6 . 1733–44 . June 1999 . 10359593 . 25365 . 10.1091/mbc.10.6.1733 .
• Suarez-Huerta N, Boeynaems JM, Communi D . Cloning, genomic organization, and tissue distribution of human Ssf-1 . Biochemical and Biophysical Research Communications . 275 . 1 . 37–42 . August 2000 . 10944437 . 10.1006/bbrc.2000.3259 .
• Communi D, Suarez-Huerta N, Dussossoy D, Savi P, Boeynaems JM . Cotranscription and intergenic splicing of human P2Y11 and SSF1 genes . The Journal of Biological Chemistry . 276 . 19 . 16561–6 . May 2001 . 11278528 . 10.1074/jbc.M009609200 . free .
• Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI . Directed proteomic analysis of the human nucleolus . Current Biology . 12 . 1 . 1–11 . January 2002 . 11790298 . 10.1016/S0960-9822(01)00650-9 . 14132033 . free . 2002CBio...12....1A .
• Duhant X, Schandené L, Bruyns C, Gonzalez NS, Goldman M, Boeynaems JM, Communi D . Extracellular adenine nucleotides inhibit the activation of human CD4+ T lymphocytes . Journal of Immunology . 169 . 1 . 15–21 . July 2002 . 12077223 . 10.4049/jimmunol.169.1.15 . free .
• Scherl A, Couté Y, Déon C, Callé A, Kindbeiter K, Sanchez JC, Greco A, Hochstrasser D, Diaz JJ . Functional proteomic analysis of human nucleolus . Molecular Biology of the Cell . 13 . 11 . 4100–9 . November 2002 . 12429849 . 133617 . 10.1091/mbc.E02-05-0271 .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–5 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . 2004PNAS..10112130B . free .
• Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R . Phosphoproteome analysis of the human mitotic spindle . Proceedings of the National Academy of Sciences of the United States of America . 103 . 14 . 5391–6 . April 2006 . 16565220 . 1459365 . 10.1073/pnas.0507066103 . 2006PNAS..103.5391N . free .
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP . A probability-based approach for high-throughput protein phosphorylation analysis and site localization . Nature Biotechnology . 24 . 10 . 1285–92 . October 2006 . 16964243 . 10.1038/nbt1240 . 14294292 .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–48 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

Notes and References

1. Welch PJ, Marcusson EG, Li QX, Beger C, Krüger M, Zhou C, Leavitt M, Wong-Staal F, Barber JR . Identification and validation of a gene involved in anchorage-independent cell growth control using a library of randomized hairpin ribozymes . Genomics . 66 . 3 . 274–83 . June 2000 . 10873382 . 10.1006/geno.2000.6230 .
2. Web site: Entrez Gene: PPAN peter pan homolog (Drosophila).
3. Pfister AS, Keil M, Kühl M . The Wnt Target Protein Peter Pan Defines a Novel p53-independent Nucleolar Stress-Response Pathway . The Journal of Biological Chemistry . 290 . 17 . 10905–18 . April 2015 . 25759387 . 4409253 . 10.1074/jbc.M114.634246 . free .
4. 10.3390/cells8080894. free. Loss of Peter Pan (PPAN) Affects Mitochondrial Homeostasis and Autophagic Flux. 2019. Dannheisig. David P.. Beck. Eileen. Calzia. Enrico. Walther. Paul. Behrends. Christian. Pfister. Astrid S.. Cells. 8. 8. 894. 31416196. 6721654.
5. Keil M, Meyer MT, Dannheisig DP, Maerz LD, Philipp M, Pfister AS . Loss of Peter Pan protein is associated with cell cycle defects and apoptotic events . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1866 . 5 . 882–895 . May 2019 . 30716409 . 10.1016/j.bbamcr.2019.01.010 . free .
6. Vitali P, Royo H, Seitz H, Bachellerie JP, Hüttenhofer A, Cavaillé J . Identification of 13 novel human modification guide RNAs . Nucleic Acids Research . 31 . 22 . 6543–51 . November 2003 . 14602913 . 275545 . 10.1093/nar/gkg849 .