Tip110 regulates the cross talk between p53 and hypoxia-inducible factor 1α under hypoxia and promotes survival of cancer cells

Khalid Amine Timani, Ying Liu, Yan Fan, Khalid Mohammad, Johnny J. He

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Hypoxia often occurs under various physiological and pathophysiological conditions, including solid tumors; it is linked to malignant transformation, metastatic progression, and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes, including cancers. Thus, in the present study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated hypoxia-inducible factor 1α (HIF-1α), likely through enhancement of its protein stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53 and HIF-1α. Expression of a p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Finally, significantly less Tip110, p53, and HIF-1α was detected in the hypoxic region of bone metastasis tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 is an important mediator in the cross talk between p53 and HIF-1α in response to hypoxic stress.

Original languageEnglish
Pages (from-to)2254-2264
Number of pages11
JournalMolecular and Cellular Biology
Volume35
Issue number13
DOIs
StatePublished - 2015

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Hypoxia-Inducible Factor 1
Cell Survival
Neoplasms
Physiological Phenomena
Protein Stability
Proteasome Endopeptidase Complex
Ubiquitin
Treatment Failure
Proteolysis
Melanoma
Cell Death
Cell Proliferation
Hypoxia
Neoplasm Metastasis
Bone and Bones
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Tip110 regulates the cross talk between p53 and hypoxia-inducible factor 1α under hypoxia and promotes survival of cancer cells. / Timani, Khalid Amine; Liu, Ying; Fan, Yan; Mohammad, Khalid; He, Johnny J.

In: Molecular and Cellular Biology, Vol. 35, No. 13, 2015, p. 2254-2264.

Research output: Contribution to journalArticle

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AU - He, Johnny J.

PY - 2015

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AB - Hypoxia often occurs under various physiological and pathophysiological conditions, including solid tumors; it is linked to malignant transformation, metastatic progression, and treatment failure or resistance. Tip110 protein plays important roles in several known physiological and pathophysiological processes, including cancers. Thus, in the present study we investigated the regulation of Tip110 expression under hypoxia. Hypoxia led to Tip110 protein degradation through the ubiquitin-proteasome system. Under hypoxia, Tip110 stabilized p53, which in return destabilized Tip110. In addition, Tip110 regulated hypoxia-inducible factor 1α (HIF-1α), likely through enhancement of its protein stability. Furthermore, Tip110 upregulated p300, a known coactivator for both p53 and HIF-1α. Expression of a p53(22/23) mutant deficient in p300 binding accelerated Tip110 degradation under hypoxia. Tip110 knockdown resulted in the inhibition of cell proliferation and cell death in the presence of p53. Finally, significantly less Tip110, p53, and HIF-1α was detected in the hypoxic region of bone metastasis tumors in a mouse model of human melanoma cells. Taken together, these results suggest Tip110 is an important mediator in the cross talk between p53 and HIF-1α in response to hypoxic stress.

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