Cells operate two major protein degradation pathways, the ubiquitination-proteasome system (UPS) pathway and the autophagy-lysosomal system (ALS) pathway, to control the stability and turnover of proteins. In UPS, proteins are selectively ubiquitinated and subsequently targeted for degradation by the 26S proteasome. Whereas, in ALS, proteins and various cytoplasmic constituents are delivered to lysosomes for catabolic turnover. One of the best target of UPS-mediated regulation of protein stability is Hypoxia-inducible factor 1 alpha (HIF-1α), which is an essential component in the transcriptional response of tumours under hypoxia. HIF-1α controls the transcription of over 60 genes involved in many aspects of cancer biology including angiogenesis, metastasis, invasion, and proliferation. HIF-1α is also degraded by ALS, although the detailed mechanism or its role in hypoxia and tumorigenesis is not yet elucidated. In this study, we investigated p300-dependent post-translational modification of HIF-1α and present a potential role of this modification in the HIF-1α regulation.