Transcriptional modulation of the rack1 gene and RACK1 expression: role of steroid hormones and significance in health and aging

Transcriptional modulation of the rack1 gene and RACK1 expression: role of steroid hormones and significance in health and aging

Research group: Marco Racchi, Erica Buoso

The Receptor for Activated C Kinase 1 (RACK1) is a scaffold protein for different kinases and membrane receptors. RACK1 can shuttle proteins to their sites of action, facilitate cross-talk among distinct signalling pathways or recruit other signalling proteins into the complexes. Therefore it is a key mediator of various pathways and is involved in various biological events including development, immune response, brain activity and cancer. Because of its importance it is of extreme significance to understand the transcriptional mechanisms governing its expression. The identification of regulatory elements in the promoter of the rack1 gene, encoding RACK1, shed some light on the transcriptional modulation of RACK1 in physiological and pathological context. Literature data support the existence of a complex hormonal balance, between glucocorticoids and androgens, in the control of RACK1 expression due to specific and complex interactions on the rack1 promoter. These and other information suggest that a better understanding of RACK1 transcriptional regulation is essential to unravel its role. The modulation of RACK1 expression in physiological or pathological conditions may be of interest in different context for example in cancer, where its multifaceted role is peculiar to most signalling cascades involved in cell proliferation, survival and invasion. In aging the decline of the immune system can be partially correlated to reduced RACK1 expression leading to reduced response to vaccination and increased susceptibility to infections and cancer.

Recent Publications:

  • Masi M, Attanzio A, Racchi M, Wolozin B, Borella S, Biundo F, Buoso E. Proteostasis Deregulation in Neurodegeneration and Its Link with Stress Granules: Focus on the Scaffold and Ribosomal Protein RACK1. Cells. 2022 Aug 19;11(16):2590.
  • Masi M, Racchi M, Travelli C, Corsini E, Buoso E. Molecular Characterization of Membrane Steroid Receptors in Hormone-Sensitive Cancers. Cells. 2021 Nov 3;10(11):2999.
  • Masi M, Garattini E, Bolis M, Di Marino D, Maraccani L, Morelli E, Grolla AA, Fagiani F, Corsini E, Travelli C, Govoni S, Racchi M, Buoso E. OXER1 and RACK1-associated pathway: a promising drug target for breast cancer progression. Oncogenesis. 2020 Dec 11;9(12):105.

Links:
https://scienzedelfarmaco.dip.unipv.it/it/ricerca/aree-di-ricerca/farmacologia
https://www.researchgate.net/profile/Marco_Racchi