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Foreign Minister Mohamed Kamel Amr submitted his resignation early Tuesday, becoming the fifth cabinet minister to leave their post amid growing protests demanding early presidential elections and the removal of President Mohamed Morsy.
Amr was appointed as part of Prime Minister Hesham Qandil's August 2012 cabinet, surviving two reshuffles in January and May 2013.
State-run news agency MENA, reporting the resignation, did not quote any sources. Foreign Ministry officials could not be reached for comment
Amr's announcement was soon followed by news that Qandil himself had offered his resignation to President Morsy.
Minister of State for Legal and Parliamentary Affairs Hatem Begato, Minister of Communications Atef Helmy, Minister of Environment Khaled Fahmy and Tourism Minister Hesham Zazou all resigned Monday.
None of the four outgoing officials belong to the president's Islamist bloc, the Muslim Brotherhood. Their resignations came as wide-scale protests demanding early presidential elections left at least 16 dead in governorates across Egypt, the health ministry reported on Monday.
The presidency, in a statement early Tuesday, rejected a 48-hour ultimatum by Defence Minister General Abdel Fattah al-Sisi to respond to the people's demands.