What’s in a name? PCGF2 #GeneOTW

Gene nomenclature is complicated and sometimes, as you’ll see, hilarious.  Take polycomb group RING finger protein 2 (PCGF2), for example.

“Polycomb group” (PcG) comes from Drosophila biology.  To the fly-ignorant, like myself, the term might sound like part of a beehive or maybe a fancy hair care tool, but the “combs” in this case refer to sex combs.  Sex combs are patches of bristles found on the forearms of male fruit flies (so they can hold on tight).  The Polycomb (Pc) gene was so named when a dominant mutation in the gene was found to cause the development of extra (hence “poly”) combs on the second and third legs of adult males.  Later, genes whose mutations enhanced or were similar to the phenotype of the Pc gene were found, and they were added to the “polycomb group.”  PcG genes are necessary to repress genes involved in cell differentiation, such as Hox genes.12

This image from Wikipedia is intended to illustrate the differences between male and female Drosophila. At first glance, I thought it was to illustrate a creepy “fly on the wall.”

“RING finger” protein domains are a class of zinc finger domains, which have finger-like protrusions (built from multiple cysteine and histine residues) that often bind zinc.  RING finger domains were first identified in the RING1 gene.  You’re not going to believe me, but R-I-N-G stands for “Really Interesting New Gene” (for a list of more-obviously hilarious gene names: thank mental_floss).  To be fair, RING1 actually is interesting (though over 20 years old!) and a PcG necessary for regulation of transcription.3

LOL, thank’s again, Wikipedia!

Just by decoding the name, PCGF2 we can guess why it is an important gene.  Another clue the gene’s original name: Mel-18, or melanoma nuclear protein 18.  In the late 1980s, Mel-18/PCGF2 was cloned from mouse melanoma cells.4 Mel-18 was later found to be a mammalian homolog of the PcG genes (and its name was changed).

PCGF2 might look like this! Rendering by Wikimedia Commons user Emw who is a fan of pretty proteins and Lowell, Massachusetts.

The expression of PCGF2 in normal tissues is limited to neural cells, and it is important for proper development of the spinal cord5  However, in almost all tumor cell lines, regardless of origin, expression is strong.67  This suggests that, like other genes involved in development, PCGF2 also plays an important role in tumor growth/suppression.  In particular, it is important for the suppression of tumorigenesis in prostate and breast cancers.891011 Despite these clues, the exact mechanism by which PCGF2 acts in neural development and tumorigenesis is still largely a mystery… and a great opportunity for a graduate student studying developmental neuroscience or cancer biology!

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2. Sparmann A, Lohuizen M van (2006). Polycomb silencers control cell fate, development and cancer. Nat Rev Cancer 6: 846–56. [↩]
3. Croce L Di, Helin K (2013). Transcriptional regulation by Polycomb group proteins. Nat Struct Mol Biol 20: 1147–55. [↩]
4. Tagawa M, Sakamoto T (1990). Expression of novel DNA-binding protein with zinc finger structure in various tumor cells. J Biol … at <http://www.jbc.org/content/265/32/20021.short>. [↩]
5. Akasaka T, Kanno M, Balling R, Mieza M a, Taniguchi M, Koseki H (1996). A role for mel-18, a Polycomb group-related vertebrate gene, during theanteroposterior specification of the axial skeleton. Development 122: 1513–22. [↩]
6. Ishida A, Asano H, Hasegawa M, Koseki H, Ono T, Yoshida MC, et al (1993). Cloning and chromosome mapping of the human Mel-18 gene which encodes a DNA-binding protein with a new “RING-finger” motif. Gene 129: 249–55. [↩]
7. Kanno M, Hasegawa M, Ishida A (1995). mel-18, a Polycomb group-related mammalian gene, encodes a transcriptional negative regulator with tumor suppressive activity. EMBO … 14: 5672–5678. [↩]
8. Guo W-J, Zeng M-S, Yadav A, Song L-B, Guo B-H, Band V, et al (2007). Mel-18 acts as a tumor suppressor by repressing Bmi-1 expression and down-regulating Akt activity in breast cancer cells. Cancer Res 67: 5083–9. [↩]
9. Wang W, Yuasa T, Tsuchiya N, Ma Z, Maita S, Narita S, et al (2009). The novel tumor-suppressor Mel-18 in prostate cancer: its functional polymorphism, expression and clinical significance. Int J Cancer 125: 2836–43. [↩]
10. Park JH, Lee JY, Shin DH, Jang KS, Kim HJ, Kong G (2011). Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway. Oncogene 30: 4578–89. [↩]
11. Lee J-Y, Park MK, Park J-H, Lee HJ, Shin DH, Kang Y, et al (2013). Loss of the polycomb protein Mel-18 enhances the epithelial-mesenchymal transition by ZEB1 and ZEB2 expression through the downregulation of miR-205 in breast cancer. Oncogene 33: 1325–1335. [↩]