Interferon-γ-induced p27KIP1 binds to and targets MYC for proteasome-mediated degradation.

Bahram, Fuad (author): Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för växtbiologi,Department of Plant Biology

Nilsson, Helén (author): Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Institutionen för translationell medicin,Klinisk patologi, Malmö,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Department of Translational Medicine,Clinical pathology, Malmö,Lund University Research Groups

Von Der Lehr, Natalie (author): Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för växtbiologi,Department of Plant Biology

Lüscher, Bernhard (author)

Castell, Alina (author): Karolinska Institutet,Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Institutionen för växtbiologi,Department of Plant Biology

(creator_code:org_t)

2015-12-20
2016
English.
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:3, s. 2837-2854

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Abstract Subject headings

The Myc oncoprotein is tightly regulated at multiple levels including ubiquitin-mediated protein turnover. We recently demonstrated that inhibition of Cdk2-mediated phosphorylation of Myc at Ser-62 pharmacologically or through interferon (IFN)-γ-induced expression of p27Kip1 (p27) repressed Myc's activity to suppress cellular senescence and differentiation. In this study we identified an additional activity of p27 to interfere with Myc independent of Ser-62 phosphorylation. p27 is required and sufficient for IFN-γ-induced turnover of Myc. p27 interacted with Myc in the nucleus involving the C-termini of the two proteins, including Myc box 4 of Myc. The C-terminus but not the Cdk2 binding fragment of p27 was sufficient for inducing Myc degradation. Protein expression data of The Cancer Genome Atlas breast invasive carcinoma set revealed significantly lower Myc protein levels in tumors with highly expressed p27 lacking phosphorylation at Thr-157 - a marker for active p27 localized in the nucleus. Further, these conditions correlated with favorable tumor stage and patient outcome. This novel regulation of Myc by IFN-γ/p27KIP1 potentially offers new possibilities for therapeutic intervention in tumors with deregulated Myc.

By the author/editor: Bahram, Fuad; Hydbring, Per; Tronnersjö, Susa ...; Zakaria, Siti Ma ...; Frings, Oliver; Fahlén, Sara; show more...; Nilsson, Helén; Goodwin, Jacob; Von Der Lehr, Na ...; Su, Yingtao; Lüscher, Bernhar ...; Castell, Alina; Larsson, Lars-Gu ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Cell Biology

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Developmental Bi ...

By the university: Lund University; Swedish University of Agricultural Sciences; Karolinska Institutet

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