The intracellular stability of DLC1 is regulated by the 26S proteasome in human hepatocellular carcinoma cell line Hep3B.
Deleted in liver cancer 1 (DLC1), a tumor suppressor gene identified in a primary human hepatocellular carcinoma, encodes a Rho GTPase-activating protein (RhoGAP). Although DLC1 expression has been studied at the transcriptional level, little is known about its regulation at the protein level. Here we show that DLC1 is an unstable protein that is degraded by the 26S proteasome in human hepatocellular carcinoma Hep3B cells. In addition, five putative PEST motifs were identified in the N-terminus of DLC1. Unexpectedly, the N-terminus of DLC1 appeared to be stable. Furthermore, deletion of any one of the five PEST motifs except PEST2 decreased the stability of the N-terminus of DLC1, which suggests that the PEST motifs may play an unrevealed role in maintaining the stability of DLC1. These data indicated that the intracellular stability of DLC1 is regulated by the 26S proteasome via its PEST motifs.
Department of Clinical Hematology, Key Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
Hong-wei
HW
Luo
Qiu-ping
QP
Luo
Ying
Y
Yuan
Xiao-ying
XY
Zhu
Shi-feng
SF
Huang
Zhi
Z
Peng
Chun-li
CL
Li
Zong-gan
ZG
Huang
Wen-li
WL
Feng
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D055550:Protein Stability; D051381:Rats; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
C112352:DLC1 protein, human; D020690:GTPase-Activating Proteins; D061988:Proteasome Inhibitors; D025521:Tumor Suppressor Proteins; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease