TY - JOUR
T1 - Ubc13 and COOH terminus of Hsp70-interacting protein (CHIP) are required for growth hormone receptor endocytosis
AU - Slotman, Johan A.
AU - Da Silva Almeida, Ana C.
AU - Hassink, Gerco C.
AU - Van De Ven, Robert H.A.
AU - Van Kerkhof, Peter
AU - Kuiken, Hendrik J.
AU - Strous, Ger J.
PY - 2012/5/4
Y1 - 2012/5/4
N2 - Growth hormone receptor (GHR) endocytosis is a highly regulated process that depends on the binding and activity of the multimeric ubiquitin ligase, SCFβTrCP (Skp Cullin F-box). Despite a specific interaction between β-transducin repeat-containing protein (βTrCP) and the GHR, and a strict requirement for ubiquitination activity, the receptor is not an obligatory target for SCFβTrCP-directed Lys48 polyubiquitination. We now show that also Lys63-linked ubiquitin chain formation is required for GHR endocytosis. We identified both the ubiquitin- conjugating enzyme Ubc13 and the ubiquitin ligase COOH terminus of Hsp70 interacting protein (CHIP) as being connected to this process. Ubc13 activity and its interaction with CHIP precede endocytosis of GHR. In addition to βTrCP, CHIP interacts specifically with the cytosolic tails of the dimeric GHR, identifying both Ubc13 and CHIP as novel factors in the regulation of cell surface availability of GHR.
AB - Growth hormone receptor (GHR) endocytosis is a highly regulated process that depends on the binding and activity of the multimeric ubiquitin ligase, SCFβTrCP (Skp Cullin F-box). Despite a specific interaction between β-transducin repeat-containing protein (βTrCP) and the GHR, and a strict requirement for ubiquitination activity, the receptor is not an obligatory target for SCFβTrCP-directed Lys48 polyubiquitination. We now show that also Lys63-linked ubiquitin chain formation is required for GHR endocytosis. We identified both the ubiquitin- conjugating enzyme Ubc13 and the ubiquitin ligase COOH terminus of Hsp70 interacting protein (CHIP) as being connected to this process. Ubc13 activity and its interaction with CHIP precede endocytosis of GHR. In addition to βTrCP, CHIP interacts specifically with the cytosolic tails of the dimeric GHR, identifying both Ubc13 and CHIP as novel factors in the regulation of cell surface availability of GHR.
UR - http://www.scopus.com/inward/record.url?scp=84860868165&partnerID=8YFLogxK
U2 - 10.1074/jbc.M111.302521
DO - 10.1074/jbc.M111.302521
M3 - Article
C2 - 22433856
AN - SCOPUS:84860868165
SN - 0021-9258
VL - 287
SP - 15533
EP - 15543
JO - Journal of biological chemistry
JF - Journal of biological chemistry
IS - 19
ER -