Delivery of cytoplasmic proteins to autophagosomes.
Autophagy represents a signaling-dependent regulated process that allows the degradation of some cellular proteins in autophagosomes, and plays a critical role in the management of cellular homeostasis under various stress conditions. In recent years, selective degradation of cytoplasmic proteins during stress has attracted considerable scientific interest. Here we examined the ability of resveratrol to induce autophagy in a variety of human cancer cell lines. We found that resveratrol-induced autophagy is accompanied by colocalization of proline-, glutamic acid-, and leucine-rich protein-1 (PELP1) with the green fluorescent protein-microtubule-associated protein 1 light chain 3 (GFP-LC3) in autophagosomes. In addition, we found that hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), a previously shown PELP1-interacting protein, is co-recruited to autophagosomes in the presence of resveratrol. Although autophagy has been assumed to be a bulk and non-selective degradation process, in recent years, evidence of selective degradation of cytosolic proteins and organelles by autophagy is mounting. These observations suggest that the interaction of the target protein(s) with the delivery protein or proteins such as HRS facilitates the transport of certain cytoplasmic proteins to autophagosomes for their selective degradation, and thus, could influence the cytoplasmic as well as nuclear functions of nuclear receptor coregulators. Since PELP1 and, perhaps, other nuclear receptor coregulators are widely dysregulated in human cancers, these findings highlight the significance of the autophagic selective degradation of PELP1 following resveratrol (or other phytoestrogens) treatment in developing future strategies to use resveratrol under cancer prevention and therapeutic settings.
Ohshiro
Kazufumi
K
Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Rayala
Suresh K
SK
El-Naggar
Adel K
AK
Kumar
Rakesh
R
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor / Q000378:metabolism; D056970:Co-Repressor Proteins; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D047629:Estrogen Receptor beta / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D000077185:Resveratrol; D015398:Signal Transduction / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
D000972:Antineoplastic Agents, Phytogenic; D056970:Co-Repressor Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D047629:Estrogen Receptor beta; D008869:Microtubule-Associated Proteins; C438485:PELP1 protein, human; D010750:Phosphoproteins; D013267:Stilbenes; D015534:Trans-Activators; D014157:Transcription Factors; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate; D000077185:Resveratrol