Citation
Turunen, Mikko, et al. "Uterine Leiomyoma-linked MED12 Mutations Disrupt Mediator-associated CDK Activity." Cell Reports, vol. 7, no. 3, 2014, pp. 654-60.
Turunen M, Spaeth JM, Keskitalo S, et al. Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity. Cell Rep. 2014;7(3):654-60.
Turunen, M., Spaeth, J. M., Keskitalo, S., Park, M. J., Kivioja, T., Clark, A. D., Mäkinen, N., Gao, F., Palin, K., Nurkkala, H., Vähärautio, A., Aavikko, M., Kämpjärvi, K., Vahteristo, P., Kim, C. A., Aaltonen, L. A., Varjosalo, M., Taipale, J., & Boyer, T. G. (2014). Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity. Cell Reports, 7(3), 654-60. https://doi.org/10.1016/j.celrep.2014.03.047
Turunen M, et al. Uterine Leiomyoma-linked MED12 Mutations Disrupt Mediator-associated CDK Activity. Cell Rep. 2014 May 8;7(3):654-60. PubMed PMID: 24746821.
TY - JOUR
T1 - Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity.
AU - Turunen,Mikko,
AU - Spaeth,Jason M,
AU - Keskitalo,Salla,
AU - Park,Min Ju,
AU - Kivioja,Teemu,
AU - Clark,Alison D,
AU - Mäkinen,Netta,
AU - Gao,Fangjian,
AU - Palin,Kimmo,
AU - Nurkkala,Helka,
AU - Vähärautio,Anna,
AU - Aavikko,Mervi,
AU - Kämpjärvi,Kati,
AU - Vahteristo,Pia,
AU - Kim,Chongwoo A,
AU - Aaltonen,Lauri A,
AU - Varjosalo,Markku,
AU - Taipale,Jussi,
AU - Boyer,Thomas G,
Y1 - 2014/04/18/
PY - 2013/10/18/received
PY - 2014/01/23/revised
PY - 2014/03/18/accepted
PY - 2014/4/22/entrez
PY - 2014/4/22/pubmed
PY - 2015/1/6/medline
SP - 654
EP - 60
JF - Cell reports
JO - Cell Rep
VL - 7
IS - 3
N2 - Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at very high frequency (∼70%) in uterine leiomyomas. However, the influence of these mutations on Mediator function and the molecular basis for their tumorigenic potential remain unknown. To clarify the impact of these mutations, we used affinity-purification mass spectrometry to establish the global protein-protein interaction profiles for both wild-type and mutant MED12. We found that uterine leiomyoma-linked mutations in MED12 led to a highly specific decrease in its association with Cyclin C-CDK8/CDK19 and loss of Mediator-associated CDK activity. Mechanistically, this occurs through disruption of a MED12-Cyclin C binding interface that we also show is required for MED12-mediated stimulation of Cyclin C-dependent CDK8 kinase activity. These findings indicate that uterine leiomyoma-linked mutations in MED12 uncouple Cyclin C-CDK8/19 from core Mediator and further identify the MED12/Cyclin C interface as a prospective therapeutic target in CDK8-driven cancers.
SN - 2211-1247
UR - https://www.unboundmedicine.com/medline/citation/24746821/Uterine_leiomyoma_linked_MED12_mutations_disrupt_mediator_associated_CDK_activity_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S2211-1247(14)00244-7
DB - PRIME
DP - Unbound Medicine
ER -