Ubiquinol-cytochrome C reductase core protein II promotes tumorigenesis by facilitating p53 degradation

Yingyan Han, Peng Wu, Zhi Wang, Zeyu Zhang, Shujuan Sun, Jia Liu, Song Gong, Peipei Gao, Tomoo Iwakuma, Miguel Angel Molina-Vila, Ping-chi B Chen, Yu Zhang, Teng Ji, Qingqing Mo, Pingbo Chen, Junbo Hu, Shixuan Wang, Jianfeng Zhou, Hua Lu, Qinglei Gao

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Ubiquinol-cytochrome C reductase core protein II (QCR2) is essential for mitochondrial functions, yet, its role in cancer development has remained elusive. Methods: The expression of QCR2 in cancer patients was assessed by immunohistochemistry. The proliferation of cancer cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. The biological function of QCR2 and PHB were determined using western blotting, RT-qPCR, microarray analysis and xenografts. The interactions between proteins and the ubiquitination of p53 were assessed by immunoprecipitation, mass spectrometry analysis and GST pull down. The subcellular location of PHB and QCR2 was assessed by immunoblotting and immunofluorescence. Finding: The expression of QCR2 is upregulated in multiple human tumors. Suppression of QCR2 inhibits cancer cell growth by activating p53 signaling and inducing p21-dependent cell cycle arrest and senescence. QCR2 directly interacts with PHB in the mitochondria. Overexpression of QCR2 inhibits PHB binding to p53 in the nucleus, and facilitates p53 ubiquitination and degradation, consequently leading to tumorigenesis. Also, increased QCR2 and decreased PHB protein levels are well correlated with decreased expression of p21 in cervical cancer tissues. Interpretation: These results identify a novel role for QCR2, together with PHB, in negative regulation of p53 stability and activity, thus promote cervical carcinogenesis. Fund: “973” Program of China, the National Science-technology Supporting Plan Projects, the National Natural Science Foundation of China, National Science and Technology Major Sub-Project and Technical Innovation Special Project of Hubei Province.

Original languageEnglish (US)
JournalEBioMedicine
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Cytochrome Reductases
Cytochromes
Oxidoreductases
Carcinogenesis
Degradation
Cells
Ubiquitination
Natural sciences
Sincalide
Neoplasms
Proteins
Mitochondria
Flow cytometry
Cell growth
Microarrays
China
Heterografts
Mass spectrometry
Tumors
Assays

Keywords

  • Degradation
  • p53
  • PHB
  • QCR2
  • Senescence
  • Tumorigenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ubiquinol-cytochrome C reductase core protein II promotes tumorigenesis by facilitating p53 degradation. / Han, Yingyan; Wu, Peng; Wang, Zhi; Zhang, Zeyu; Sun, Shujuan; Liu, Jia; Gong, Song; Gao, Peipei; Iwakuma, Tomoo; Molina-Vila, Miguel Angel; Chen, Ping-chi B; Zhang, Yu; Ji, Teng; Mo, Qingqing; Chen, Pingbo; Hu, Junbo; Wang, Shixuan; Zhou, Jianfeng; Lu, Hua; Gao, Qinglei.

In: EBioMedicine, 01.01.2019.

Research output: Contribution to journalArticle

Han, Y, Wu, P, Wang, Z, Zhang, Z, Sun, S, Liu, J, Gong, S, Gao, P, Iwakuma, T, Molina-Vila, MA, Chen, PB, Zhang, Y, Ji, T, Mo, Q, Chen, P, Hu, J, Wang, S, Zhou, J, Lu, H & Gao, Q 2019, 'Ubiquinol-cytochrome C reductase core protein II promotes tumorigenesis by facilitating p53 degradation', EBioMedicine. https://doi.org/10.1016/j.ebiom.2019.01.002
Han, Yingyan ; Wu, Peng ; Wang, Zhi ; Zhang, Zeyu ; Sun, Shujuan ; Liu, Jia ; Gong, Song ; Gao, Peipei ; Iwakuma, Tomoo ; Molina-Vila, Miguel Angel ; Chen, Ping-chi B ; Zhang, Yu ; Ji, Teng ; Mo, Qingqing ; Chen, Pingbo ; Hu, Junbo ; Wang, Shixuan ; Zhou, Jianfeng ; Lu, Hua ; Gao, Qinglei. / Ubiquinol-cytochrome C reductase core protein II promotes tumorigenesis by facilitating p53 degradation. In: EBioMedicine. 2019.
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abstract = "Background: Ubiquinol-cytochrome C reductase core protein II (QCR2) is essential for mitochondrial functions, yet, its role in cancer development has remained elusive. Methods: The expression of QCR2 in cancer patients was assessed by immunohistochemistry. The proliferation of cancer cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. The biological function of QCR2 and PHB were determined using western blotting, RT-qPCR, microarray analysis and xenografts. The interactions between proteins and the ubiquitination of p53 were assessed by immunoprecipitation, mass spectrometry analysis and GST pull down. The subcellular location of PHB and QCR2 was assessed by immunoblotting and immunofluorescence. Finding: The expression of QCR2 is upregulated in multiple human tumors. Suppression of QCR2 inhibits cancer cell growth by activating p53 signaling and inducing p21-dependent cell cycle arrest and senescence. QCR2 directly interacts with PHB in the mitochondria. Overexpression of QCR2 inhibits PHB binding to p53 in the nucleus, and facilitates p53 ubiquitination and degradation, consequently leading to tumorigenesis. Also, increased QCR2 and decreased PHB protein levels are well correlated with decreased expression of p21 in cervical cancer tissues. Interpretation: These results identify a novel role for QCR2, together with PHB, in negative regulation of p53 stability and activity, thus promote cervical carcinogenesis. Fund: “973” Program of China, the National Science-technology Supporting Plan Projects, the National Natural Science Foundation of China, National Science and Technology Major Sub-Project and Technical Innovation Special Project of Hubei Province.",
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AU - Han, Yingyan

AU - Wu, Peng

AU - Wang, Zhi

AU - Zhang, Zeyu

AU - Sun, Shujuan

AU - Liu, Jia

AU - Gong, Song

AU - Gao, Peipei

AU - Iwakuma, Tomoo

AU - Molina-Vila, Miguel Angel

AU - Chen, Ping-chi B

AU - Zhang, Yu

AU - Ji, Teng

AU - Mo, Qingqing

AU - Chen, Pingbo

AU - Hu, Junbo

AU - Wang, Shixuan

AU - Zhou, Jianfeng

AU - Lu, Hua

AU - Gao, Qinglei

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Ubiquinol-cytochrome C reductase core protein II (QCR2) is essential for mitochondrial functions, yet, its role in cancer development has remained elusive. Methods: The expression of QCR2 in cancer patients was assessed by immunohistochemistry. The proliferation of cancer cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. The biological function of QCR2 and PHB were determined using western blotting, RT-qPCR, microarray analysis and xenografts. The interactions between proteins and the ubiquitination of p53 were assessed by immunoprecipitation, mass spectrometry analysis and GST pull down. The subcellular location of PHB and QCR2 was assessed by immunoblotting and immunofluorescence. Finding: The expression of QCR2 is upregulated in multiple human tumors. Suppression of QCR2 inhibits cancer cell growth by activating p53 signaling and inducing p21-dependent cell cycle arrest and senescence. QCR2 directly interacts with PHB in the mitochondria. Overexpression of QCR2 inhibits PHB binding to p53 in the nucleus, and facilitates p53 ubiquitination and degradation, consequently leading to tumorigenesis. Also, increased QCR2 and decreased PHB protein levels are well correlated with decreased expression of p21 in cervical cancer tissues. Interpretation: These results identify a novel role for QCR2, together with PHB, in negative regulation of p53 stability and activity, thus promote cervical carcinogenesis. Fund: “973” Program of China, the National Science-technology Supporting Plan Projects, the National Natural Science Foundation of China, National Science and Technology Major Sub-Project and Technical Innovation Special Project of Hubei Province.

AB - Background: Ubiquinol-cytochrome C reductase core protein II (QCR2) is essential for mitochondrial functions, yet, its role in cancer development has remained elusive. Methods: The expression of QCR2 in cancer patients was assessed by immunohistochemistry. The proliferation of cancer cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. The biological function of QCR2 and PHB were determined using western blotting, RT-qPCR, microarray analysis and xenografts. The interactions between proteins and the ubiquitination of p53 were assessed by immunoprecipitation, mass spectrometry analysis and GST pull down. The subcellular location of PHB and QCR2 was assessed by immunoblotting and immunofluorescence. Finding: The expression of QCR2 is upregulated in multiple human tumors. Suppression of QCR2 inhibits cancer cell growth by activating p53 signaling and inducing p21-dependent cell cycle arrest and senescence. QCR2 directly interacts with PHB in the mitochondria. Overexpression of QCR2 inhibits PHB binding to p53 in the nucleus, and facilitates p53 ubiquitination and degradation, consequently leading to tumorigenesis. Also, increased QCR2 and decreased PHB protein levels are well correlated with decreased expression of p21 in cervical cancer tissues. Interpretation: These results identify a novel role for QCR2, together with PHB, in negative regulation of p53 stability and activity, thus promote cervical carcinogenesis. Fund: “973” Program of China, the National Science-technology Supporting Plan Projects, the National Natural Science Foundation of China, National Science and Technology Major Sub-Project and Technical Innovation Special Project of Hubei Province.

KW - Degradation

KW - p53

KW - PHB

KW - QCR2

KW - Senescence

KW - Tumorigenesis

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