PEG10

What is PEG10 Protein?

The PEG10 protein, short for Paternally Expressed Gene 10, comes from an old retrovirus that became part of our genetic makeup. While it can't replicate on its own anymore, PEG10 still plays a big role in biology, influencing things like embryonic development and cancer progression. In mice, it's crucial for placenta formation and the differentiation of fat cells, and removing the gene can lead to embryonic death. PEG10 is also found in high levels in various cancers, such as liver, breast, and lung cancer, where it helps tumor cells grow and avoid dying. Additionally, PEG10 is linked to Angelman syndrome, with its expression being controlled by the UBE3A protein.

What is the Function of PEG10 Protein?

PEG10 is a paternally expressed gene that plays significant roles in both adult and embryonic tissues, with notable activity in the placenta. It has two key isoforms—the shorter one contains a zinc finger motif common to gag proteins of many retroviruses and participates in interactions with the TGF-beta receptor family, while the longer isoform is associated with the protease domain of pol proteins seen in some retroviruses. PEG10 is a gene that is expressed from the paternal allele, and it plays a role in many important cell processes such as the growth, specialization, and programmed cell death of cells. It's very similar in many mammals, highlighting its important role in the development of embryos. Mice missing PEG10 tend not to survive early on due to problems with the placenta. Additionally, when PEG10 is produced in excess, it has been associated with some cancers like liver cancer and a type of leukemia. Changes in how much PEG10 is expressed have also been connected to conditions like preeclampsia.

PEG10 Related Signaling Pathway

PEG10 is heavily involved in several key signaling pathways that are vital for cell development and functioning. One of the main pathways it's tied to is the TGF-beta signaling pathway, where it interacts with receptors and can influence cell proliferation and differentiation. In terms of disease, altered PEG10 signaling through its links to these pathways can play a role in various cancers, such as influencing the progression of hepatic cancers. Its expression levels can affect apoptosis and cell migration, highlighting its importance in both normal cellular activities and pathological conditions. This makes PEG10 an intriguing target for research, especially in cancer therapy, where deciphering its pathway involvement might offer new treatment options.

PEG10 Related Diseases

PEG10 is intricately linked with several diseases, mainly due to its role in regulating cell processes. It's often highlighted in cancer discussions, especially in liver cancer (hepatocellular carcinoma) and types of leukemia. Its overexpression is a significant marker in these malignancies, suggesting it might drive cancer progression. Beyond cancer, PEG10's altered expression levels also appear in conditions like preeclampsia, where changes in its activity are observed in the placenta. This makes PEG10 relevant in both oncology and obstetrics due to its impact on cellular growth and development.

Bioapplications of PEG10

PEG10 is drawing attention in various scientific and clinical fields due to its unique properties. In basic research, it serves as a model for studying genomic imprinting and retrotransposon-derived genes, helping scientists understand more about gene regulation and expression. Clinically, PEG10's role in cancer progression, particularly in liver cancer and leukemia, makes it a potential target for innovative cancer therapies, where it might help in developing drugs that hinder its overexpression. In industrial applications, its characteristics as a paternally imprinted gene offer opportunities to explore its utility in biotechnological processes. Moreover, as it can influence cell proliferation and differentiation, PEG10 is considered for tissue engineering and regenerative medicine research, where modulating its activity might aid in developing improved therapeutic techniques.

Case Study 1: Saratov V. et al. Sci Rep. 2022

Researchers have been delving into Ewing sarcoma (ES), the second most common childhood bone and soft tissue tumor. This aggressive cancer is marked by a specific chromosomal swap, t(11;22), producing the challenging-to-target fusion protein EWS-FLI1, which reshapes protein expression by toggling numerous genes on or off. To gain insight into this, the team set up a CRISPR activation system in SKNMC cell lines, examining a focused library of 871 genes suppressed by EWS-FLI1. Among the key findings, several TGFβ pathway genes stood out, with PEG10 showing promise due to its strong antiproliferative effects. Further investigation showed that ramping up PEG10 led to cell death. Additionally, non-canonical TGFβ pathways like RAF/MEK/ERK, MKK/JNK, and MKK/P38, which are linked to apoptosis and autophagy, were significantly triggered when PEG10 was overexpressed.

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  Fig1. PEG10, SGCE and EWS-FLI1 protein levels in SKNMC SAM D8 cells overexpressing PEG10.
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  Fig2. EWS-FLI1, PEG10 and SGCE protein levels in SKNMC cells with the inducible EWS-FLI1 shRNA construct upon induction for 24, 48 and 72 h.

Case Study 2: Golda M. et al. Int J Mol Sci. 2020

Researchers have been exploring the role of Paternally expressed gene 10 (PEG10), a human gene derived from a retrotransposon. PEG10 mRNA produces two protein variants: a Gag-like protein and a Gag-Pol-like polyprotein, the latter through a retroviral-style frameshift. The RF2PEG10 protein has a protease domain with a sequence typical of retroviral aspartic proteases, but its role isn't clear. To investigate, researchers engineered a frameshift mutant of the polyprotein to compare with the original. In experiments with HEK293T and HaCaT cells, they used plasmids to express either the original or mutant forms. The findings showed that the mutant increased cell proliferation but harmed cell viability, suggesting the PEG10 protease may be crucial in cell growth and stopping cell death.

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  Fig3. Expression of different forms of RF1/RF2PEG10 in HEK293T cells was detected with anti-PEG10 antibody.
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  Fig4. Western blot analysis revealed ubiquitination of PEG10.

PEG10 has several biochemical functions, for example, DNA binding,poly(A) RNA binding,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PEG10 itself. We selected most functions PEG10 had, and list some proteins which have the same functions with PEG10. You can find most of the proteins on our site.

Function	Related Protein
DNA binding	HOXB6A,SUPT6H,TSG101,CSDE1,OASL1,GTF2F2A,DEAF1,CARF,RORCA,ZFP367
zinc ion binding	RNF43,BMP1B,MMP23B,GDA,RFPL3,TRIM14,RNF2,BIRC8,TRIM36,SUV39H2
protein binding	SLC25A6,LGALS8,PPIB,CHMP4C,ARL2BP,STXBP4,MTX2,DUSP14,MCM6,THAP11
poly(A) RNA binding	NXF2,REPIN1,RPS17L,SRSF11,DDX24,PRRC2A,NOP2,PWP2,FLYWCH2,KHDRBS3

PEG10 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PEG10 here. Most of them are supplied by our site. Hope this information will be useful for your research of PEG10.

FAM127A;LDOC1;CALCOCO2;FAM127C;SIAH1;TOLLIP;LAMTOR5;CLIP4;LNX2