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Scully KM, Lahmy R, Signaevskaia L, et al. E47 Governs the MYC-CDKN1B/p27. Cell Mol Gastroenterol Hepatol. 2018;6(2):181-198doi: 10.1016/j.jcmgh.2018.05.002.
Scully, K. M., Lahmy, R., Signaevskaia, L., Sasik, R., Medal, R., Kim, H., French, R., James, B., Wu, Y., Lowy, A. M., & Itkin-Ansari, P. (2018). E47 Governs the MYC-CDKN1B/p27. Cellular and molecular gastroenterology and hepatology, 6(2), 181-198. https://doi.org/10.1016/j.jcmgh.2018.05.002
Scully, Kathleen M, et al. "E47 Governs the MYC-CDKN1B/p27." Cellular and molecular gastroenterology and hepatology vol. 6,2 (2018): 181-198. doi: https://doi.org/10.1016/j.jcmgh.2018.05.002
Scully KM, Lahmy R, Signaevskaia L, Sasik R, Medal R, Kim H, French R, James B, Wu Y, Lowy AM, Itkin-Ansari P. E47 Governs the MYC-CDKN1B/p27. Cell Mol Gastroenterol Hepatol. 2018 May 16;6(2):181-198. doi: 10.1016/j.jcmgh.2018.05.002. eCollection 2018. PMID: 30003124; PMCID: PMC6039985.
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Cell Mol Gastroenterol Hepatol. 2018 May 16;6(2):181-198. doi: 10.1016/j.jcmgh.2018.05.002. eCollection 2018.

E47 Governs the MYC-CDKN1B/p27.

Cellular and molecular gastroenterology and hepatology

Kathleen M Scully, Reyhaneh Lahmy, Lia Signaevskaia, Roman Sasik, Rachel Medal, Heejung Kim, Randall French, Brian James, Yifan Wu, Andrew M Lowy, Pamela Itkin-Ansari

Affiliations

  1. Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
  2. Center for Computational Biology and Bioinformatics, School of Medicine.
  3. Department of Surgery, Division of Surgical Oncology, Moores Cancer Center.
  4. Genomics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
  5. Department of Pediatrics, University of California San Diego, La Jolla, California.

PMID: 30003124 PMCID: PMC6039985 DOI: 10.1016/j.jcmgh.2018.05.002

Abstract

BACKGROUND & AIMS: Oncogenic mutations in KRAS, coupled with inactivation of p53, CDKN2A/p16

METHODS: RNA sequencing was used to profile E47-dependent transcriptomes in 5 PDA cell lines. Gene Ontology analysis identified cell-cycle control as the most altered pathway. Small interfering RNA/short hairpin RNA knockdown, small-molecule inhibitors, and viral expression were used to examine the function of E47-dependent genes in cell-cycle arrest. Cell morphology, expression of molecular markers, and senescence-associated β-galactosidase activity assays identified cellular senescence.

RESULTS: E47 uniformly inhibited PDA cell-cycle progression by decreasing expression of MYC, increasing the level of CDKN1B/p27

CONCLUSIONS: E47 governs a highly conserved network of cell-cycle control genes, including MYC, CDKN1B/p27

Keywords: CDK, cyclin-dependent kinase; CDKN1B/p27KIP1, CDKN1B/p27Kinase Inhibitory Protein 1; CDKN2A/p16INK4A, CDKN2A/p16Inhibitor of CDK 4A; CEBP-α, CCAAT/enhancer binding protein alpha; CENP-A, centromere protein A; CIP, Cyclin-Dependent Kinase Inhibitor 1; Cell Cycle; DDR, DNA damage response; ERK, extracellular signal–regulated kinase; GO, Gene Ontology; INK, Inhibitor of CDK; KIP, Kinase Inhibitory Protein; MSCV, murine stem cell virus; OIS, oncogene-induced senescence; PCR, polymerase chain reaction; PDA, pancreatic ductal adenocarcinoma; Pancreatic Ductal Adenocarcinoma; RB, retinoblastoma; RNA-seq, RNA sequencing; SA-βgal, senescence-associated β-galactosidase; SKP, S-phase Kinase-associated; Senescence; bHLH; bHLH, basic helix-loop-helix; lfdr, local false discovery rate; mRNA, messenger RNA; shRB, short hairpin RNA directed against RB; shRNA, short hairpin RNA; si-p27, small interfering RNA directed against p27

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