The International Journal of Developmental Biology

Int. J. Dev. Biol. 65: 377 - 382 (2021)

Vol 65, Issue 4-5-6

Special Issue: Developmental Biology in Ibero-America - Part 2

LIN-35 beyond its classical roles: its function in the stress response

Published: 26 August 2020

Alan A. González-Rangel and Rosa E. Navarro*

Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, México


The pocket protein family controls several cellular functions such as cell cycle, differentiation, and apoptosis, among others. However, its role in stress has been poorly explored. The roundworm Caenorhabditis elegans is a simple model organism whose genes are highly conserved during evolution. C. elegans has only one pocket protein, LIN-35; a retinoblastoma protein (pRB)-related protein similar to p130. To control the expression of some of its targets, LIN-35 interacts with E2F-DP (E2 transcription factor/dimerization partner complex) transcription factors and LIN-52, a member of SynMUV (Synthetic Muv) complex. Together, these proteins form the DRM complex, which is also known as the DREAM complex in mammals. In this review, we will focus on the role of LIN-35 and its partners in the stress response. It has been shown that LIN-35 is required to control starvation in L1 and L4 larval stages, and to induce starvation-induced germ apoptosis. Remarkably, during L1 starvation, insulin/IGF-1 receptor signaling (IIS), as well as the pathogenic, toxin, and oxidative stress-responsive genes, are repressed by LIN-35. The lack of lin-35 also triggers a downregulation of oxidative stress genes. Recent works showed that lin-35 and hpl-2 mutant animals showed enhanced resistance to UPRER. Additionally, hpl-2 mutant animals also exhibited upregulation of autophagic genes, suggesting that SynMuv/DRM proteins participate in this process. Finally, lin-35(n745) mutant animals overexpressed hsp-6, a chaperone that participated in the UPRmt. All of these data demonstrate that LIN-35 and its partners play an important role during the stress response.


LIN-35, stress, DREAM complex, Rb, DRM complex

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