PHC3, a component of the hPRC-H complex, associates with 2A7E during G0 and is lost in osteosarcoma tumors

Abstract

Polyhomeotic-like 3 (PHC3) is a ubiquitously expressed member of the polycomb gene family and part of the human polycomb complex hPRC-H. We found that in normal cells PHC3 associated with both hPRC-H complex components and with the transcription factor E2F6. In differentiating and confluent cells, PHC3 and E2F6 showed nuclear colocalization in a punctate pattern that resembled the binding of polycomb bodies to heterochromatin. This punctate pattern was not seen in proliferating cells suggesting that PHC3 may be part of an E2F6-polycomb complex that has been shown to occupy and silence target promoters in G 0 . Previous loss of heterozygosity (LoH) analyses had shown that the region containing PHC3 underwent frequent LoH in primary human osteosarcoma tumors. When we examined normal bone and human osteosarcoma tumors, we found loss of PHC3 expression in 36 of 56 osteosarcoma tumors. Sequence analysis revealed that PHC3 was mutated in nine of 15 primary osteosarcoma tumors. These findings suggest that loss of PHC3 may favor tumorigenesis by potentially disrupting the ability of cells to remain in G 0 .

Identification of protein O-GlcNAcylation sites using electron transfer dissociation mass spectrometry on native peptides

“…Polyhomeoticlike protein 3 is part of the polycomb PRC1 complex involved in long-term gene silencing (33), and the protein is believed to be a tumor suppressor protein (34). Another tumor suppressor protein, particularly associated with breast and ovarian cancer, is EMSY, a transcriptional repressor of the BRCA2 gene (35).…”

A comprehensive ChIP–chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members

“…Also, E2F6 has been shown to interact with PcG proteins, which are known to regulate HOX genes. For example, E2F6 has been shown to interact with Polyhomeotic-like (PHC3) (Isono et al 2005;Deshpande et al 2007) and with BMI1 (Trimarchi et al 2001), two members of the hPRC-H family of PcG proteins. One study copurified E2F6 with EZH2 (Attwooll et al 2005) and we have previously shown that Ezh2 binds to the promoters of hundreds of homeobox genes ).…”

Mutational analysis of Polycomb genes in solid tumours identifies PHC3 amplification as a possible cancer-driving genetic alteration

“…To the best of our knowledge, PHC3 genomic amplification and mRNA upregulation have never been described before. However, PHC3 has been found to be downregulated in human sarcomas, where it acts as a tumour suppressor (Deshpande et al , 2007). …”

“…PhC proteins bridge distant chromatin templates, thereby recruiting PRC1 to selected loci (Lavigne et al , 2004). Currently, three PhC isoforms are known, with different tissue distribution and partially overlapping functions (Deshpande et al , 2007). PRC1 has been implicated in tumorigenesis and progression of several cancer types.…”