2. Academic Validation
  3. Degradation of AF1Q by chaperone-mediated autophagy

Degradation of AF1Q by chaperone-mediated autophagy

  • Exp Cell Res. 2014 Sep 10;327(1):48-56. doi: 10.1016/j.yexcr.2014.05.013.
Peng Li 1,  Min Ji 1,  Fei Lu 1,  Jingru Zhang 1,  Huanjie Li 2,  Taixing Cui 2,  Xing Li Wang 2,  Dongqi Tang 3,  Chunyan Ji 4
Affiliations

Affiliations

  • 1 Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012, P.R. China.
  • 2 Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012, P.R. China.
  • 3 Research Center for Cell Therapy, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012, P.R. China; Center for Stem Cell & Regenerative Medicine, The Second Hospital of Shandong University, Jinan 250033, P.R. China. Electronic address: tangdq@sdu.edu.cn.
  • 4 Department of Hematology, Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan 250012, P.R. China. Electronic address: jichunyan@sdu.edu.cn.
PMID: 24880125 DOI: 10.1016/j.yexcr.2014.05.013
Abstract

AF1Q, a mixed lineage leukemia gene fusion partner, is identified as a poor prognostic biomarker for pediatric acute myeloid leukemia (AML), adult AML with normal cytogenetic and adult myelodysplastic syndrome. AF1Q is highly regulated during hematopoietic progenitor differentiation and development but its regulatory mechanism has not been defined clearly. In the present study, we used pharmacological and genetic approaches to influence chaperone-mediated Autophagy (CMA) and explored the degradation mechanism of AF1Q. Pharmacological inhibitors of lysosomal degradation, such as chloroquine, increased AF1Q levels, whereas activators of CMA, including 6-aminonicotinamide and nutrient starvation, decreased AF1Q levels. AF1Q interacts with HSPA8 and LAMP-2A, which are core components of the CMA machinery. Knockdown of HSPA8 or LAMP-2A increased AF1Q protein levels, whereas overexpression showed the opposite effect. Using an amino acid deletion AF1Q mutation plasmid, we identified that AF1Q had a KFERQ-like motif which was recognized by HSPA8 for CMA-dependent proteolysis. In conclusion, we demonstrate for the first time that AF1Q can be degraded in lysosomes by CMA.

Keywords

AF1Q; Chaperone-mediated autophagy; Protein degradation; macroautophagy.

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