Altered receptor trafficking in Huntingtin Interacting Protein 1-transformed cells.
The clathrin-associated protein, Huntingtin Interacting Protein 1 (HIP1), is overexpressed in multiple human epithelial tumors. Here, we report that HIP1 is a novel oncoprotein that transforms cells. HIP1-transformed cells, in contrast to RasV12-transformed cells, have dysregulation of multiple receptors involved in clathrin trafficking. Examples include upregulation of the epidermal growth factor receptor (EGFR) and the transferrin receptor. Furthermore, accumulation of transferrin and EGF in the HIP1-transformed cells was increased, and breast tumors that had EGFR expressed also had HIP1 upregulated. Thus, HIP1 overexpression promotes tumor formation and is associated with a general alteration in receptor trafficking. HIP1 is the first endocytic protein to be directly implicated in tumor formation.
Rao
Dinesh S
DS
Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan Medical School, Ann Arbor 48109, USA.
Bradley
Sarah V
SV
Kumar
Priti D
PD
Hyun
Teresa S
TS
Saint-Dic
Djenann
D
Oravecz-Wilson
Katherine
K
Kleer
Celina G
CG
Ross
Theodora S
TS
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D002453:Cell Cycle; D002455:Cell Division; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism
D002352:Carrier Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; C489536:Hip1 protein, mouse; D014168:Transferrin; D066246:ErbB Receptors