Cell Cycle Progression Effects of Albumin

<p>Progression through G₁ phase of the cell cycle is controlled largely by growth factors in early G₁ and by nutrients in late G₁ indicating sufficient raw material for cell division. We previously mapped a late G₁ cell cycle checkpoint for lipids upstream from a mammalian target of rapamycin complex 1 (mTORC1)-mediated checkpoint and downstream from a mid-G₁ checkpoint known as the Restriction point. We therefore investigated a role for lipids in progression through late G₁ into S-phase. Quiescent BJ-hTERT human fibroblasts primed back into G1 with FBS treatment, were treated with a mixture of lipids and carrier bovine serum albumin (BSA) along with [3H]-thymidine deoxyribose ([3H]-TdR) to monitor progression into S-phase. Surprisingly, BSA by itself, was more effective than FBS in promoting progression to S-phase – the lipids had no impact on progression. While insulin strongly stimulated mTORC1 activity, it did not impact [3H]-TdR incorporation. We show that though BSA only sustained low levels of mTORC1 activity, rapamycin strongly inhibited BSA-induced progression to S-phase. BSA treatment promoted mitosis evident from an increase in cell number after treatment, but not progression through a second G₁. Thus, after priming quiescent cells with FBS, albumin was sufficient to promote progression into S-phase. The BSA did not compensate as a source of free amino acids in that amino acids were present in the culture media and additional increasing doses of exogenous amino acids did not affect DNA synthesis. We propose that the presence of albumin – the most abundant protein in serum – signals to the cell a broader availability and variety of amino acids over abundance.</p>

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biology

Grantor

The Graduate School and University Center of The City University of New York

Year dc:date.available

2021

Author dc:creator

• Uddin, Sharmeen

Advisor dc:contributor.advisor

• David Foster

Committee members dc:contributor.committeemember

• Patricia Rockwell
• Diego Loayza
• Anjana Saxena
• Richard Possemato

• Biology
• Cancer Biology
• Medicine and Health Sciences
• Cancer Metabolism
• Cell Cycle Regulation

Repository record dc:identifier

https://academicworks.cuny.edu/gc_etds/4126

OAI identifier oai:identifier

oai:academicworks.cuny.edu:gc_etds-5182