Identification of tumor suppressor gene, TUSC1, as an autophagy-specific binding partner to Beclin1

Monday, October 24, 2011 — Poster Session I
Noon – 2:00 p.m.	Natcher Conference Center	NCI	CANCER-9

Authors

• C Garber
• Z Shan
• J Simmons
• C Husko
• J Wiest

Abstract

Lung cancer continues to be the leading cause of cancer mortality in the world. We begin by characterizing the function of tumor suppressor candidate 1 gene (TUSC1) in regulating autophagy. Autophagy is a mechanism of tumor suppression and chemoresistance, providing a means to mitigate cellular metabolic stress and maintain genomic integrity. TUSC1 is shown to bind the essential autophagic protein Beclin1. The effects of TUSC1 expression on autophagy were delineated by immunoblotting for markers of autophagy: microtubule associated protein 1 light chain 3 (LC3) and p62/SQSTM1. Additionally, confocal microscopy illustrates the effects of TUSC1 on autophagosomal formation by LC3 visualization while displaying altered levels of the DNA damage repair marker histone protein H2AX. Consistent with an increase in autophagy, we observe that the expression of TUSC1 decreases SQSTM1 while increasing the conversion of LC3I to LC3II. Results were reproduced in the absence of the critical autophagy gene, Beclin 1, suggesting TUSC1 can function independent of Beclin1. Finally, data showing a decrease in perinuclear H2AX in the presence of TUSC1, thereby reducing cellular stress, is consistent with the tumor suppressive role of autophagy. This report provides functional insight into how loss of TUSC1 may potentiate tumor progression through decreased autophagy.

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