Alternative titles; symbols
HGNC Approved Gene Symbol: JMY
Cytogenetic location: 5q14.1 Genomic coordinates (GRCh38) : 5:79,236,131-79,327,211 (from NCBI)
JMY is a stress-responsive protein involved in regulation of p53 (TP53; 191170) activity. JMY also has actin-nucleating activity and plays a role in cell motility (summary by Coutts et al., 2011).
The p300 (EP300; 602700)/CBP (CREBBP; 600140) proteins, which act as coactivators for diverse transcription factors, participate in regulating p53 (TP53; 191170) activity. Using a yeast 2-hybrid screening approach, Shikama et al. (1999) identified a novel cofactor for p300 that facilitated the p53 response by augmenting p53-dependent transcription and apoptosis. This gene, which the authors designated JMY, encodes a 983-amino acid protein containing S/T-P motifs in its N-terminal region, an adenovirus E1A CR2-like motif, EVQFEILKCEE, in its central region, and a proline-rich C-terminal region. In addition, the JMY protein has 2 p300-binding domains, one located in the N-terminal region (residues 1 to 119), where it overlaps the S/T-P-rich region, and the other located in the central region (residues 469 to 558). Shikama et al. (1999) also identified potential JMY splice variants encoding protein isoforms.
Coutts et al. (2011) found that epitope-tagged JMY colocalized with actin in the cytoplasm and periphery of transfected U2OS cells.
Shikama et al. (1999) showed that JMY and p300 associated in physiologic conditions. During the cellular stress response, the p300/JMY complex was recruited to activated p53. The BAX gene (600040) was efficiently activated by JMY, and JMY protein isoforms that arose through alternative splicing altered the functional outcome of the p53 response. Shikama et al. (1999) concluded that the p300/JMY coactivator complex plays a central role in facilitating the p53 response.
Coutts et al. (2011) found that JMY mRNA and protein expression were upregulated during hypoxia in human cell lines in an HIF1-alpha (HIF1A; 603348)-dependent manner. HIF1-alpha directly upregulated JMY via HIF1-alpha response elements in the JMY promoter. Knockdown of JMY markedly decreased cell migration in 3-dimensional culture. Deferoxamine (DFO), a hypoxia mimic, further reduced migration of JMY-depleted cells; however, overexpression of JMY following DFO treatment augmented cell mobility. In hypoxic U87 xenografts in nude mice, Jmy expression coincided with increased Hif1-alpha activity.
By FISH, Shikama et al. (1999) mapped the JMY gene to chromosome 5q13.2.
Coutts, A. S., Pires, I. M., Weston, L., Buffa, F. M., Milani, M., Li, J.-L., Harris, A. L., Hammond, E. M., La Thangue, N. B. Hypoxia-driven cell motility reflects the interplay between JMY and HIF-1-alpha. Oncogene 30: 4835-4842, 2011. [PubMed: 21625218] [Full Text: https://doi.org/10.1038/onc.2011.188]
Shikama, N., Lee, C.-W., France, S., Delavaine, L., Lyon, J., Krstic-Demonacos, M., La Thangue, N. B. A novel cofactor for p300 that regulates the p53 response. Molec. Cell 4: 365-376, 1999. [PubMed: 10518217] [Full Text: https://doi.org/10.1016/s1097-2765(00)80338-x]