Acetylation-mediated degradation of HSD17B4 regulates the progression of prostate cancer.

Aging
Huichao HuangYongheng Chen

Abstract

Steroidogenic enzymes are crucial in prostate cancer (PCa) progression. 17β-Hydroxysteroid dehydrogenase type 4 (HSD17B4), encoded by HSD17B4, lacks catalytic capacity in androgen metabolism. Now the detailed role and molecular mechanism of PCa development are largely unknown. Here we showed that the expression of HSD17B4 was increased in PCa tissues compared to paired paratumor tissues. HSD17B4 knockdown in PCa cells significantly suppressed its proliferation, migration and invasion, while overexpressing HSD17B4 had opposite effects. Mechanistically, we found that the protein level of HSD17B4 was regulated by its acetylation at lysine 669(K669). Dihydroxytestosterone (DHT) treatment increased HSD17B4 acetylation and then promoted its degradation via chaperone-mediated autophagy (CMA). SIRT3 directly interacted with HSD17B4 to inhibit its acetylation and enhance its stability. In addition, we identified CREBBP as a regulator of the K669 acetylation and degradation of HSD17B4, affecting PC cell proliferation, migration and invasion. Notably, in PCa tissues and paired paratumor tissues, the level of HSD17B4 was negatively correlated with its K669 acetylation. Taken together, this study identified a novel role of HSD17B4 in PCa pr...Continue Reading

References

Aug 1, 1990·Trends in Biochemical Sciences·J F Dice
Jan 15, 1983·International Journal of Cancer. Journal International Du Cancer·J GerdesH Stein
May 19, 1997·The Journal of Cell Biology·F A AgarraberesJ F Dice
Dec 16, 1997·Proceedings of the National Academy of Sciences of the United States of America·J V SwinnenG Verhoeven
Jun 18, 1999·The Journal of Clinical Endocrinology and Metabolism·M A EnglishM Hewison
Oct 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·Patrick OnyangoAndrew P Feinberg
Apr 4, 2007·Autophagy·J Fred Dice
Feb 29, 2008·Nature·Noboru MizushimaDaniel J Klionsky
Jul 2, 2008·Breast Cancer Research and Treatment·Robin L JonesMitchell Dowsett
Dec 23, 2008·Molecular and Cellular Endocrinology·Krishan K RasiahVanessa M Hayes
Mar 3, 2009·Annals of the New York Academy of Sciences·Trevor M Penning, Michael C Byrns
Oct 28, 2009·Trends in Endocrinology and Metabolism : TEM·Ana Maria Cuervo
Dec 8, 2009·Cancer Cell·Gerhardt AttardJohann S de Bono
Feb 16, 2010·The Lancet Oncology·Rinat YerushalmiKaren A Gelmon
Jul 22, 2010·Endocrine-related Cancer·Marion T Weigel, Mitch Dowsett
Nov 15, 2011·Cell·Noboru Mizushima, Masaaki Komatsu
Mar 29, 2012·Molecular and Cellular Endocrinology·Sean M GreenPeter S Nelson
Jul 4, 2012·Trends in Cell Biology·Susmita Kaushik, Ana Maria Cuervo
Jan 22, 2013·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Jun 12, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Adegoke O AdenijiTrevor M Penning
Oct 15, 2013·Autophagy·François StricherSylviane Muller
Jun 4, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Trevor M Penning
Jun 25, 2016·World Journal of Gastroenterology : WJG·Ting LiuYong-Heng Chen

❮ Previous
Next ❯

Citations

Mar 2, 2021·Frontiers in Oncology·Javiera RiosMauricio Budini
Nov 19, 2021·Expert Review of Proteomics·Orlando Morales-TarréSergio Encarnación-Guevara

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE70770

Methods Mentioned

BETA
acetylation
transfection
coimmunoprecipitation
co-IP

Software Mentioned

GEPIA
ImageJ
Xena HUGO probeMap
GEPIA ( Gene Expression Profiling Interactive Analysis )

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.