TY - JOUR
T1 - VHL and hypoxia signaling
T2 - Beyond HIF in cancer
AU - Zhang, Jing
AU - Zhang, Qing
N1 - Funding Information:
Acknowledgments: Jing Zhang is supported by a DoD BCRP Breakthrough Fellowship Award (W81XWH-17-1-0016). Qing Zhang is supported by grants from the National Cancer Institute (R01CA211732, R21CA223675). Qing Zhang also received a career development award from the DoD (W81XWH-15-1-0599). Qing Zhang is a V R21SCchAo2la2r3,6 K7i5m).mQeli nSgchZolhaar,n Kgoamlseon rCeacreeievreCdaataclyasret eArwdaervdeeleo,pamndeMntaarywKarady FfrooumndtahteioDn oADwa(Wrd8ee1.XWH-15-1-0599). Qing Zhang is a V Scholar, Kimmel Scholar, Komen Career Catalyst Awardee, and Mary Kay Foundation Awardee. Author Contributions: Jing Zhang and Qing Zhang conceived and wrote this review together. Author Contributions: Jing Zhang and Qing Zhang conceived and wrote this review together. Conflicts of Interest: The authors declare no conflict of interest. Conflicts of Interest: The authors declare no conflict of interest.
Publisher Copyright:
© 2018 by the authors.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-κB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer.
AB - Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-κB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer.
KW - Hypoxia
KW - VHL
KW - ccRCC
UR - http://www.scopus.com/inward/record.url?scp=85056271743&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056271743&partnerID=8YFLogxK
U2 - 10.3390/biomedicines6010035
DO - 10.3390/biomedicines6010035
M3 - Review article
C2 - 29562667
AN - SCOPUS:85056271743
SN - 2227-9059
VL - 6
JO - Biomedicines
JF - Biomedicines
IS - 1
M1 - 35
ER -