• Research
  • PAF complex in the transcriptional and post-transcriptional regulation and its relevance to cancer.
    The PAF complex (PAFc) is a multifaceted RNA polymerase II associated factor that is composed of PAF1, CTR9, CDC73, LEO1, RTF1 and SKI81. It functions to recruit diverse regulatory proteins of transcription, like histone modifying enzymes or elongation factors, and thereby controlling every steps of transcription in the nucleus1.
    1) We are specifically interested in the signal- and locus- specific roles of PAFc. Earlier we reported that PAFc exerts IL-6 and IL-1β specific transcriptional regulation at the specific target locus2-4. Upon IL-6 stimulation, PAFc selectively activates expression of the acute phase response proteins, while restricts induction of the paused immediate early genes2,3. We aim to understand the regulatory mechanism of PAFc that selects specific target locus and modification of PAFc that allows signal dependency.
    2) CDC73 is a composing component of PAFc that usually functions in the nucleus. We recently reported a secondary complex with CDC73, which is distinct to conventional PAFc. It is composed with eEF1g-Ski8-CDC73 and functions to control stability of mature mRNA in the cytosol5. This complex binds to the mature form of p53 mRNA and brings it to the exosome for degradation5. We aim to understand the molecular and physiological role of cytosolic CDC73 as well as its regulation
    3) Human CDC73 (also known as parafibromin) is reported to function as a tumor suppressor protein, and its loss of function mutation is highly associated with hyperparathyroidism jaw tumors. PAF1 (also known as PD2 (pancreatic differentiation 2)) is also overexpressed in pancreatic cancer cells and has oncogenic potential6. Although PAFc is highly associated with various cancers, detailed molecular mechanism and physiological roles of each PAFc component are not fully understood. We aim to understand the link between PAFc and cancer.

    1. Jaehning, J. A. The Paf1 complex: platform or player in RNA polymerase II transcription? Biochim Biophys Acta 1799, 379-388 (2010).
    2. Youn, M. Y. et al. hCTR9, a component of Paf1 complex, participates in the transcription of interleukin 6-responsive genes through regulation of STAT3-DNA interactions. J Biol Chem 282, 34727-34734 (2007).
    3. Yoo, H. S., Seo, J. H. & Yoo, J. Y. CTR9, a component of PAF complex, controls elongation block at the c-Fos locus via signal-dependent regulation of chromatin-bound NELF dissociation. PLoS One 8 (2013).
    4. Kim, N., Sun, H. Y., Youn, M. Y. & Yoo, J. Y. IL-1beta-specific recruitment of GCN5 histone acetyltransferase induces the release of PAF1 from chromatin for the de-repression of inflammatory response genes. Nucleic Acids Res 41, 4495-4506 (2013).
    5. Jo, J. H., Chung, T. M., Youn, H. & Yoo, J. Y. Cytoplasmic parafibromin/hCdc73 targets and destabilizes p53 mRNA to control p53-mediated apoptosis. Nat Commun 5, 5433 (2014).
    6. Chaudhary, K., Deb, S., Moniaux, N., Ponnusamy, M. P. & Batra, S. K. Human RNA polymerase II-associated factor complex: dysregulation in cancer. Oncogene 26, 7499-7507 (2007).