Редактирование: CBX4

E3 SUMO-protein ligase CBX4 (EC 2.3.2.-) (Chromobox protein homolog 4) (Polycomb 2 homolog) (Pc2) (hPc2)

==Publications==

{{medline-entry
|title=Biological functions of chromobox (CBX) proteins in stem cell self-renewal, lineage-commitment, cancer and development.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32979540
|abstract=Epigenetic regulatory proteins support mammalian development, cancer, aging and tissue repair by controlling many cellular processes including stem cell self-renewal, lineage-commitment and senescence in both skeletal and non-skeletal tissues. We review here our knowledge of epigenetic regulatory protein complexes that support the formation of inaccessible heterochromatin and suppress expression of cell and tissue-type specific biomarkers during development. Maintenance and formation of heterochromatin critically depends on epigenetic regulators that recognize histone 3 lysine trimethylation at residues K9 and K27 (respectively, H3K9me3 and H3K27me3), which represent transcriptionally suppressive epigenetic marks. Three chromobox proteins (i.e., [[CBX1]], [[CBX3]] or CBX5) associated with the heterochromatin protein 1 (HP1) complex are methyl readers that interpret H3K9me3 marks which are mediated by H3K9 methyltransferases (i.e., [[SUV39H1]] or SUV39H2). Other chromobox proteins (i.e., [[CBX2]], [[CBX4]], [[CBX6]], [[CBX7]] and CBX8) recognize H3K27me3, which is deposited by Polycomb Repressive Complex 2 (PRC2; a complex containing [[SUZ12]], [[EED]], RBAP46/48 and the methyl transferases [[EZH1]] or EZH2). This second set of CBX proteins resides in [[PRC1]], which has many subunits including other polycomb group factors (PCGF1, [[PCGF2]], [[PCGF3]], PCGF4, [[PCGF5]], PCGF6), human polyhomeotic homologs (HPH1, HPH2, HPH3) and E3-ubiquitin ligases (RING1 or RING2). The latter enzymes catalyze the subsequent mono-ubiquitination of lysine 119 in H2A (H2AK119ub). We discuss biological, cellular and molecular functions of CBX proteins and their physiological and pathological activities in non-skeletal cells and tissues in anticipation of new discoveries on novel roles for CBX proteins in bone formation and skeletal development.

|keywords=* Aging
* Bone
* CBX1
* CBX2
* CBX3
* CBX4
* CBX5
* CBX6
* CBX7
* CBX8
* Cancer
* Chromatin
* Development
* Epigenetics
* H3K27me3
* H3K9me3
* Lineage-commitment
* Osteoblast
* Senescence
* Stem cell
|full-text-url=https://sci-hub.do/10.1016/j.bone.2020.115659
}}
{{medline-entry
|title=Maintenance of Nucleolar Homeostasis by [[CBX4]] Alleviates Senescence and Osteoarthritis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30917318
|abstract=[[CBX4]], a component of polycomb repressive complex 1 (PRC1), plays important roles in the maintenance of cell identity and organ development through gene silencing. However, whether [[CBX4]] regulates human stem cell homeostasis remains unclear. Here, we demonstrate that [[CBX4]] counteracts human mesenchymal stem cell (hMSC) aging via the maintenance of nucleolar homeostasis. [[CBX4]] protein is downregulated in aged hMSCs, whereas [[CBX4]] knockout in hMSCs results in destabilized nucleolar heterochromatin, enhanced ribosome biogenesis, increased protein translation, and accelerated cellular senescence. [[CBX4]] maintains nucleolar homeostasis by recruiting nucleolar protein fibrillarin (FBL) and heterochromatin protein KRAB-associated protein 1 (KAP1) at nucleolar rDNA, limiting the excessive expression of rRNAs. Overexpression of [[CBX4]] alleviates physiological hMSC aging and attenuates the development of osteoarthritis in mice. Altogether, our findings reveal a critical role of [[CBX4]] in counteracting cellular senescence by maintaining nucleolar homeostasis, providing a potential therapeutic target for aging-associated disorders.
|mesh-terms=* Animals
* Cell Nucleolus
* Cellular Senescence
* Chromosomal Proteins, Non-Histone
* Gene Knockout Techniques
* Genetic Therapy
* HEK293 Cells
* Homeostasis
* Humans
* Ligases
* Male
* Mesenchymal Stem Cells
* Mice, Inbred C57BL
* Mice, Inbred NOD
* Osteoarthritis
* Polycomb-Group Proteins
|keywords=* CBX4
* CRISPR/Cas9
* aging
* epigenetics
* gene editing
* heterochromatin
* nucleolus
* osteoarthritis
* rDNA
* stem cell
|full-text-url=https://sci-hub.do/10.1016/j.celrep.2019.02.088
}}